CAZypedia - User contributions [en-ca]

Glycoside Hydrolase Family 93

2019-03-05T14:47:00Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:overallsurf.png|thumb|250px|right|'''Figure 1. Cartoon representation of the overall structure of Arb93A''' (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>Carapito2009</cite>.''' Propeller colored by from N to C-terminus (blue to red) and arabinobiose depicted as balls and sticks.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose (Fig. 1) <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 2). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 3). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
[[Image:242den.png|thumb|right|200px|'''Figure 2. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2ydt 2YDT] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]
[[File:62 araf chembiochem-17.jpg|thumb|right|200px|'''Figure 3. Electron density for hydroximolactone inhibitor bound to the active site of Arb93A (PDB ID [{{PDBlink}}5m1z 5M1Z].<cite>Coyle2017</cite>''']]

The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose . The active site is located in a deep acidic L-shaped crevice at the center of the beta-propeller (Fig. 1). Structures of the wild-type or E242A mutant enzyme in complex with iminoarabinobiose were solved at 1.6 and 1.85 angstrom resolution respectively as well as a complex with a shape mimic inhibitor and demonstrated ring distorsion (Fig. 2-3). <cite>GoddardBorger2011 Coyle2017</cite>

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:45:56Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:overallsurf.png|thumb|250px|right|'''Figure 1. Cartoon representation of the overall structure of Arb93A''' (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>Carapito2009</cite>.''' Propeller colored by from N to C-terminus (blue to red) and arabinobiose depicted as balls and sticks.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose (Fig. 1) <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 2). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 3). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
[[Image:242den.png|thumb|right|200px|'''Figure 2. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2ydt 2YDT] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]
[[File:62 araf chembiochem-17.jpg|thumb|right|200px|'''Figure 3. '''Electron density for hydroximolactone inhibitor bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}5m1z 5M1Z].<cite>Coyle2017</cite>''']]

The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose . The active site is located in a deep acidic L-shaped crevice at the center of the beta-propeller (Fig. 1). Structures of the wild-type or E242A mutant enzyme in complex with iminoarabinobiose were solved at 1.6 and 1.85 angstrom resolution respectively as well as a complex with a shape mimic inhibitor and demonstrated ring distorsion (Fig. 2-3). <cite>GoddardBorger2011 Coyle2017</cite>

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:44:50Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:overallsurf.png|thumb|200px|right|'''Figure 1'''. Cartoon representation of the overall structure of Arb93A''' (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>Carapito2009</cite>.''' Propeller colored by from N to C-terminus (blue to red) and arabinobiose depicted as balls and sticks.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose (Fig. 1) <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 2). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 3). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
[[Image:242den.png|thumb|right|200px|'''Figure 2. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2ydt 2YDT] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]
[[File:62 araf chembiochem-17.jpg|thumb|right|200px|'''Figure 3. '''Electron density for hydroximolactone inhibitor bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}5m1z 5M1Z].<cite>Coyle2017</cite>''']]

The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose . The active site is located in a deep acidic L-shaped crevice at the center of the beta-propeller (Fig. 1). Structures of the wild-type or E242A mutant enzyme in complex with iminoarabinobiose were solved at 1.6 and 1.85 angstrom resolution respectively as well as a complex with a shape mimic inhibitor and demonstrated ring distorsion (Fig. 2-3). <cite>GoddardBorger2011 Coyle2017</cite>

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:43:27Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:overallsurf.png|thumb|200px|right|'''Figure 1. '''Cartoon representation of the overall structure of Arb93A''' (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>Carapito2009</cite>. Propeller colored by from N to C-terminus (blue to red) and arabinobiose depicted as balls and sticks.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose (Fig. 1) <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 2). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 3). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
[[Image:242den.png|thumb|right|200px|'''Figure 2. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2ydt 2YDT] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]
[[File:62 araf chembiochem-17.jpg|thumb|right|200px|'''Figure 3. '''Electron density for hydroximolactone inhibitor bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}5m1z 5M1Z].<cite>Coyle2017</cite>''']]

The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose . The active site is located in a deep acidic L-shaped crevice at the center of the beta-propeller (Fig. 1). Structures of the wild-type or E242A mutant enzyme in complex with iminoarabinobiose were solved at 1.6 and 1.85 angstrom resolution respectively as well as a complex with a shape mimic inhibitor and demonstrated ring distorsion (Fig. 2-3). <cite>GoddardBorger2011 Coyle2017</cite>

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:43:00Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:overallsurf.png|thumb|200px|right|'''Figure 1. '''Cartoon representation of the overall structure of Arb93A''' (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>Carapito2009</cite>. Propeller colored by from N to C-terminus (blue to red) and arabinobiose depicted as balls and sticks.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose (Fig. 1) <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 2). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 3). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
[[Image:overallsurf.png|thumb|200px|right|'''Figure 3. '''Cartoon representation of the overall structure of Arb93A''' (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>Carapito2009</cite>. Propeller colored by from N to C-terminus (blue to red) and arabinobiose depicted as balls and sticks.]]

The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose . The active site is located in a deep acidic L-shaped crevice at the center of the beta-propeller (Fig. 3). Structures of the wild-type or E242A mutant enzyme in complex with iminoarabinobiose were solved at 1.6 and 1.85 angstrom resolution respectively as well as a complex with a shape mimic inhibitor and demonstrated ring distorsion (Fig. 1-2). <cite>GoddardBorger2011 Coyle2017</cite>

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:40:01Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:242den.png|thumb|right|200px|'''Figure 1. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2ydt 2YDT] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[File:62 araf chembiochem-17.jpg|thumb|200px|'''Figure 2. '''Electron density for hydroximolactone inhibitor bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}5m1z 5M1Z].<cite>Coyle2017</cite>''']]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
[[Image:overallsurf.png|thumb|200px|right|'''Figure 3. '''Cartoon representation of the overall structure of Arb93A''' (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>Carapito2009</cite>. Propeller colored by from N to C-terminus (blue to red) and arabinobiose depicted as balls and sticks.]]

The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose . The active site is located in a deep acidic L-shaped crevice at the center of the beta-propeller (Fig. 3). Structures of the wild-type or E242A mutant enzyme in complex with iminoarabinobiose were solved at 1.6 and 1.85 angstrom resolution respectively as well as a complex with a shape mimic inhibitor and demonstrated ring distorsion (Fig. 1-2). <cite>GoddardBorger2011 Coyle2017</cite>

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

File:Overallsurf.png

2019-03-05T14:38:42Z

Annabelle Varrot:

Glycoside Hydrolase Family 93

2019-03-05T14:29:51Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:242den.png|thumb|right|200px|'''Figure 1. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2ydt 2YDT] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[File:62 araf chembiochem-17.jpg|thumb|200px|'''Figure 2. '''Electron density for hydroximolactone inhibitor bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}5m1z 5M1Z].<cite>Coyle2017</cite>''']]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
[[Image:Arb93a.png|thumb|200px|right|'''Figure 3. '''Cartoon representation of the overall structure of Arb93A''' (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>Carapito2009</cite>. Propeller colored by blade and arabinobiose depicted as balls and sticks.]]

The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose (Fig. 3). Structures of the wild-type or E242A mutant enzyme in complex with imminoarabinobiose were solved at 1.6 and 1.85 ansgtrom resolution respectively (Fig. 1) as well as a complew with shape mimic inhibitor (Fig. 2) and demonstrated ring distorsion. <cite>GoddardBorger2011 Coyle2017</cite>

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:28:17Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:242den.png|thumb|right|200px|'''Figure 1. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[File:62 araf chembiochem-17.jpg|thumb|200px|'''Figure 2. '''Electron density for hydroximolactone inhibitor bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}5m1z 5M1Z].<cite>Coyle2017</cite>''']]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
[[Image:Arb93a.png|thumb|200px|right|'''Figure 3. '''Cartoon representation of the overall structure of Arb93A''' (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>Carapito2009</cite>. Propeller colored by blade and arabinobiose depicted as balls and sticks.]]

The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose (Fig. 3). Structures of the wild-type or E242A mutant enzyme in complex with imminoarabinobiose were solved at 1.6 and 1.85 ansgtrom resolution respectively (Fig. 1) as well as a complew with shape mimic inhibitor (Fig. 2) and demonstrated ring distorsion. <cite>GoddardBorger2011 Coyle2017</cite>

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:24:24Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:242den.png|thumb|right|200px|'''Figure 1. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[File:62 araf chembiochem-17.jpg|thumb|200px|'''Figure 2. '''Electron density for hydroximolactone inhibitor bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}5m1z 5M1Z].<cite>Coyle2017</cite>''']]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose (Fig. 3). Structures of the wild-type or E242A mutant enzyme in complex with imminoarabinobiose were solved at 1.6 and 1.85 ansgtrom resolution respectively (Fig. 1) as well as a complew with shape mimic inhibitor (Fig. 2) and demonstrated ring distorsion. <cite>GoddardBorger2011 Coyle2017</cite>

[[Image:Arb93a.png|overall|300px|right|'''Figure 3.''' Cartoon representation of the overall structure of Arb93A colored by blade.]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:22:46Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:242den.png|thumb|right|250px|'''Figure 1. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[File:62 araf chembiochem-17.jpg|thumb|200px|'''Figure 2. '''Electron density for hydroximolactone inhibitor bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}5m1z 5M1Z].<cite>Coyle2017</cite>''']]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose (Fig. 3). Structures of the wild-type or E242A mutant enzyme in complex with imminoarabinobiose were solved at 1.6 and 1.85 ansgtrom resolution respectively (Fig. 1) as well as a complew with shape mimic inhibitor (Fig. 2) and demonstrated ring distorsion. <cite>GoddardBorger2011 Coyle2017</cite>

[[Image:Arb93a.png|overall|300px|right|'''Figure 3.''' Cartoon representation of the overall structure of Arb93A colored by blade.]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:21:38Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:242den.png|thumb|right|250px|'''Figure 1. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[File:62 araf chembiochem-17.jpg|thumb|250px|'''Figure 2. '''Electron density for hydroximolactone inhibitor bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}5m1z 5M1Z] <cite>Coyle2017</cite>.''']]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose (Fig. 3). Structures of the wild-type or E242A mutant enzyme in complex with imminoarabinobiose were solved at 1.6 and 1.85 ansgtrom resolution respectively (Fig. 1) as well as a complew with shape mimic inhibitor (Fig. 2) and demonstrated ring distorsion. <cite>GoddardBorger2011 Coyle2017</cite>

[[Image:Arb93a.png|overall|300px|right|'''Figure 3.''' Cartoon representation of the overall structure of Arb93A colored by blade.]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:20:48Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:242den.png|thumb|right|300px|'''Figure 1. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2w5o 2W5O] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[File:62 araf chembiochem-17.jpg|thumb|300px|'''Figure 2. '''Electron density for hydroximolactone inhibitor bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}5m1z 5M1Z] cite>Coyle2017</cite>.''']]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose (Fig. 3). Structures of the wild-type or E242A mutant enzyme in complex with imminoarabinobiose were solved at 1.6 and 1.85 ansgtrom resolution respectively (Fig. 1) as well as a complew with shape mimic inhibitor (Fig. 2) and demonstrated ring distorsion. <cite>GoddardBorger2011 Coyle2017</cite>

[[Image:Arb93a.png|overall|300px|right|'''Figure 3.''' Cartoon representation of the overall structure of Arb93A colored by blade.]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:18:39Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:242den.png|thumb|right|300px|'''Figure 1. Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A (PDB ID [{{PDBlink}}2w50 2W5O] <cite>GoddardBorger2011</cite>.''' Hydrogens bond are represented as dash lines.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[File:62 araf chembiochem-17.jpg|thumb|300px|'''Figure 2. '''Electron density for hydroximolactone inhibitor bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}5m1z 5M1Z] cite>Coyle2017</cite>.''' Hydrogens bond are represented as dash lines and 2Fobs–Fcalc electron density at 0.95 eA<sup>-3</sup>]]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose (Fig. 3). Structures of the wild-type or E242A mutant enzyme in complex with imminoarabinobiose were solved at 1.6 and 1.85 ansgtrom resolution respectively (Fig. 1) as well as a complew with shape mimic inhibitor (Fig. 2) and demonstrated ring distorsion. <cite>GoddardBorger2011 Coyle2017</cite>

[[Image:Arb93a.png|overall|300px|right|'''Figure 3.''' Cartoon representation of the overall structure of Arb93A colored by blade.]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T14:15:31Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
[[Image:242den.png|iminoarabinobiose|300px|right|'''Figure 1.''' '''Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A''' (PDB ID [{{PDBlink}}2w50 2W5O] <cite>GoddardBorger2011</cite>. Hydrogens bond are represented as dash lines.]]

GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|300px|'''Figure 2.''' Electron density for hydroximolactone inhibitor bound to the active site of Arb93A (PDB ID [{{PDBlink}}5m1z 5M1Z]cite>Coyle2017</cite>. Hydrogens bond are represented as dash lines and 2Fobs–Fcalc electron density at 0.95 eA<sup>-3</sup>]]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose (Fig. 3). Structures of the wild-type or E242A mutant enzyme in complex with imminoarabinobiose were solved at 1.6 and 1.85 ansgtrom resolution respectively (Fig. 1) as well as a complew with shape mimic inhibitor (Fig. 2) and demonstrated ring distorsion. <cite>GoddardBorger2011 Coyle2017</cite>

[[Image:Arb93a.png|overall|300px|right|'''Figure 3.''' Cartoon representation of the overall structure of Arb93A colored by blade.]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T11:24:30Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[Image:242den.png|inhibitor|300px|'''Figure 1.''' Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A. Hydrogens bond are represented as dash lines and 2Fobs–Fcalc electron density at 0.35 eA<sup>-3</sup>]]
[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|300px|'''Figure 2.''' Electron density for hydroximolactone inhibitor bound to the active site of Arb93A. Hydrogens bond are represented as dash lines and 2Fobs–Fcalc electron density at 0.95 eA<sup>-3</sup>]]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E (Fig. 3). <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The wild-type structure was solved at 2.05 angstrom resolution in complex with arabinobiose (Fig. 3). Structures of the wild-type or E242A mutant enzyme in complex with imminoarabinobiose were solved at 1.6 and 1.85 ansgtrom resolution respectively (Fig. 1) as well as a complew with shape mimic inhibitor (Fig. 2) and demonstrated ring distorsion. <cite>GoddardBorger2011 Coyle2017</cite>

[[Image:Arb93a.png|overall|300px|right|'''Figure 3.''' Cartoon representation of the overall structure of Arb93A colored by blade.]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T11:19:11Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[Image:242den.png|inhibitor|300px|'''Figure 1.''' Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A. Hydrogens bond are represented as dash lines and 2Fobs–Fcalc electron density at 0.35 eA<sup>-3</sup>]]
[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|300px|'''Figure 2.''' Electron density for hydroximolactone inhibitor bound to the active site of Arb93A. Hydrogens bond are represented as dash lines and 2Fobs–Fcalc electron density at 0.95 eA<sup>-3</sup>]]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The overall structure is depicted in the left figure with the arabinobiose bound to the active site. <cite>Carapito2009</cite> Electron density for an deoxyiminosugar and a shape mimic inhibitor with their interaction with Arb93A demonstrating ring distorsion are shown in the middle and left figures. <cite>GoddardBorger2011 Coyle2017</cite>

[[Image:Arb93a.png|overall|300px|right|'''Figure 3.''' Cartoon representation of the overall structure of Arb93A colored by blade.]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-05T11:15:26Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases (Fig. 1). <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate (Fig. 2). They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

[[Image:242den.png|inhibitor|300px|'''Figure 1.''' Electron density for deoxyiminoarabinobiose bound to the active site of Arb93A. Hydrogens bond are represented as dash lines and 2Fobs–Fcalc electron density at 0.35 eA<sup>-3</sup>]]
[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|300px|'''Figure 2.''' Electron density for hydroximolactone inhibitor bound to the active site of Arb93A. Hydrogens bond are represented as dash lines and 2Fobs–Fcalc electron density at 0.95 eA<sup>-3</sup>]]

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The overall structure is depicted in the left figure with the arabinobiose bound to the active site. <cite>Carapito2009</cite> Electron density for an deoxyiminosugar and a shape mimic inhibitor with their interaction with Arb93A demonstrating ring distorsion are shown in the middle and left figures. <cite>GoddardBorger2011 Coyle2017</cite>

[[Image:Arb93a.png|overall|500px]]
[[Image:242den.png|inhibitor|500px]]
[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|400px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-04T15:40:29Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The overall structure is depicted in the left figure with the arabinobiose bound to the active site. <cite>Carapito2009</cite> Electron density for an deoxyiminosugar and a shape mimic inhibitor with their interaction with Arb93A demonstrating ring distorsion are shown in the middle and left figures. <cite>GoddardBorger2011 Coyle2017</cite>

[[Image:Arb93a.png|overall|500px]]
[[Image:242den.png|inhibitor|500px]]
[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|400px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-04T15:39:55Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The overall structure is depicted in the left figure with the arabinobiose bound to the active site. <cite>Carapito2009</cite> Electron density for an deoxyiminosugar and a shape mimic inhibitor with their interaction with Arb93A demonstrating ring distorsion are shown in the middle and left figures. <cite>GoddardBorger2011 Coyle2017</cite>

[[Image:Arb93a.png|overall|400px]]
[[Image:242den.png|inhibitor|400px]]
[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|400px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-04T15:39:32Z

Annabelle Varrot: /* Kinetics and Mechanism */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp<sup>2</sup> hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The overall structure is depicted in the left figure with the arabinobiose bound to the active site. <cite>Carapito2009</cite> Electron density for an deoxyiminosugar and a shape mimic inhibitor with their interaction with Arb93A demonstrating ring distorsion are shown in the middle and left figures. <cite>Goddard-Borger2011 coyle2017</cite>

[[Image:Arb93a.png|overall|400px]]
[[Image:242den.png|inhibitor|400px]]
[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|400px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-04T15:38:59Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp2 hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The overall structure is depicted in the left figure with the arabinobiose bound to the active site. <cite>Carapito2009</cite> Electron density for an deoxyiminosugar and a shape mimic inhibitor with their interaction with Arb93A demonstrating ring distorsion are shown in the middle and left figures. <cite>Goddard-Borger2011 coyle2017</cite>

[[Image:Arb93a.png|overall|400px]]
[[Image:242den.png|inhibitor|400px]]
[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|400px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-04T15:36:55Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp2 hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite> The overall structure is depicted in the left figure with the arabinobiose bound to the active site. <cite>Carapito2009</cite> Electron density for an deoxyiminosugar and a shape mimic inhibitor with their interaction with Arb93A demonstrating ring distorsion are shown in the middle and left figures. <cite>Goddard-Borger 2111, coyle2017</cite>

[[Image:Arb93a.png|overall|400px]]
[[Image:242den.png|inhibitor|400px]]
[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|400px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-04T15:32:06Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp2 hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite>

[[Image:Arb93a.png|overall|400px]]
[[Image:242den.png|inhibitor|400px]]
[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|400px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-04T15:31:16Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp2 hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite>

[[Image:Arb93a.png|overall|400px]]
[[Image:242den.png|inhibitor|400px]]

[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|300px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-04T15:30:53Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp2 hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite>

[[Image:Arb93a.png|overall|400px]]
[[Image:242den.png|inhibitor|400px]]

[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|400px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-04T15:29:41Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp2 hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite>

[[Image:Arb93a.png|overall]]
[[Image:242den.png|inhibitor|500px]]

[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|500px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-04T15:29:22Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp2 hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite>

[[Image:Arb93a.jpg|overall]]
[[Image:242den.png|inhibitor|500px]]

[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|500px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

File:Arb93a.png

2019-03-04T15:28:46Z

Annabelle Varrot: Overall structure of ARb93A with depiction of arabinobiose in the active site

Overall structure of ARb93A with depiction of arabinobiose in the active site

Glycoside Hydrolase Family 93

2019-03-04T15:26:56Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp2 hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite>

[[Image:Overalla4.jpg|Arb93A]]
[[Image:242den.png|inhibitor|500px]]

[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor|500px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2019-03-04T15:26:14Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp2 hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite>

[[Image:Overalla4.jpg|Arb93A]]
[[Image:242den.png|inhibitor|500px]]

[[File:62 araf chembiochem-17.jpg|sp<sup>2</sup> inhibitor]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

File:62 araf chembiochem-17.jpg

2019-03-04T15:23:17Z

Annabelle Varrot:

Glycoside Hydrolase Family 93

2019-03-04T15:21:18Z

Annabelle Varrot:

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>Sakamoto2001 Carapito2009</cite>, EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>Sakamoto2004</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose <cite>Carapito2009 Sogabe2011</cite>. α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>GoddardBorger2011</cite> Potent shape mimic inhibitors exploiting sp2 hybridization at the anomeric carbon have been recently synthetized as well as a chromogenic substrate. They are useful tools to assist further biochemical studies on L-arabinanases. <cite>Coyle2017</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>Carapito2009</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>Sogabe2011</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>Carapito2009 Sogabe2011</cite>, The catalytic machinery is however very different from that of sialidases. <cite>Gaskell1995</cite>

[[Image:Overalla4.jpg|Arb93A]]
[[Image:242den.png|inhibitor|500px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>Sakamoto2004</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>Carapito2009</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>Carapito2009</cite>

== References ==
<biblio>

#Sakamoto2001 pmid=11425761
#Carapito2009 pmid=19269961
#Sakamoto2004 pmid=15342117
#Sogabe2011 pmid=21543843
#GoddardBorger2011 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-9686. //''Note: Due to a problem with PubMed data, this reference is not automatically formatted. Please see these links out:'' [http://dx.doi.org/10.1039/C1CC13675E DOI:10.1039/C1CC13675E] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21773614 PMID: 21773614]
#Coyle2017 pmid=28266777
#Gaskell1995 pmid=8591030
</biblio>


[[Category:Glycoside Hydrolase Families|GH093]]

Glycoside Hydrolase Family 93

2011-09-08T16:38:03Z

Annabelle Varrot: /* Three-dimensional structures */

{{CuratorApproved}}
* [[Author]]: [[User:Annabelle Varrot|Annabelle Varrot]]
* [[Responsible Curator]]: [[User:Annabelle Varrot|Annabelle Varrot]]

<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Glycoside Hydrolase Family GH93'''
|-
|'''Clan'''
|GH-E
|-
|'''Mechanism'''
|retaining
|-
|'''Active site residues'''
|known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |http://www.cazy.org/fam/GH93.html
|}
</div>

== Substrate specificities ==
The characterized [[glycoside hydrolases]] of family GH93 are known to hydrolyse linear α-1,5-L-arabinan. <cite>1</cite>, <cite>2</cite>,
EC:3.2.1-.

== Kinetics and Mechanism ==
GH93 enzymes are [[exo]]-acting enzymes that only release arabinobiose from the non-reducing end of α-1,5-L-arabinan. These enzymes are proposed to be [[retaining]] enzymes based on the net retention of the configuration of the anomeric carbon is proposed from the products of the transglycosylation activity of the protein Abnx from ''Penicillium chrysogenum'' <cite>3</cite>. This proposal obtained support from the crystal structures of the Arb93A enzyme from ''Fusarium graminearum'' and Abnx both in complex with arabinobiose. <cite>2</cite>,<cite>4</cite> α-L-Arabinofuranosylated pyrrolidines were shown to be good inhibitors of Arb93A. The Arb93A complex structure with a deoxyiminosugar equivalent of arabinobiose revealed a <sup>4</sup>T<sub>N</sub> twist conformation expected for the Michaelis complex, as seen for several retaining GH51 α-L-arabinofuranosidases. <cite>5</cite>

== Catalytic Residues ==
From the crystal structure of Arb93A, Glu170 and Glu242 are proposed to act as [[catalytic nucleophile]] and [[general acid/base]] respectively. Mutagenesis experiment support their role in catalysis and they are strictly conserved among the family members. <cite>2</cite> Recent structures and mutagenesis studies for the arabinanase Abnx from ''Penicillium chrysogenum 31B'' strengthened this assignment. Mutations to alanine or glutamine of their equivalent Glu174 and Glu246 lead to inactive enzyme. <cite>4</cite>

== Three-dimensional structures ==
The crystal structure of Arb93A reveals a six-bladed β-propeller fold characteristic of sialidases of [[clan]] GH-E. <cite>2,4</cite>, The catalytic machinery is however very different from that of sialidases. <cite>6</cite>

[[Image:Overalla4.jpg|Arb93A]]
[[Image:242den.png|inhibitor|500px]]

== Family Firsts ==
'''First sterochemistry determination'''

This was determined with the ''Penicillium chrysogenum'' Abxn enzyme using <sup>1</sup>H-NMR to identify the transglycosylation products <cite>3</cite>

'''First [[catalytic nucleophile]] identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>2</cite>

'''First [[general acid/base]] residue identification'''
This was proposed based on the structure of ''Fusarium graminearum'' Arb93A <cite>2</cite>

'''First 3-D structure'''
Determined for ''Fusarium graminearum'' Arb93A by Carapito and co-workers <cite>2</cite>

== References ==
<biblio>

#1 pmid=11425761
#2 pmid=19269961
#3 pmid=15342117
#4 Sogabe Y, Kitatani T, Yamaguchi A, Kinoshita T, Adachi H, Takano K, Inoue T, Mori Y, Matsumura H, Sakamoto T and Tad, T. ''High-resolution structure of exo-arabinanase from
Penicillium chrysogenum.'' Acta Crystallogr D Biol Crystallogr 2011 May;67(Pt 5):415-22. doi:10.1107/S0907444911006299 pmid:21543843.
#5 Goddard-Borger ED, Carapito R, Jeltsch JM, Phalip V, Stick RV, Varrot A. ''α-l-Arabinofuranosylated pyrrolidines as arabinanase inhibitors''. Chem Commun 2011 Sep 14;47(34):9684-6. doi:10.1039/C1CC13675E pmid:21773614.
#6 pmid=8591030

</biblio>

[[Category:Glycoside Hydrolase Families|GH093]]

File:242den.png

2011-09-08T16:33:39Z

Annabelle Varrot: Arb93A E242A with EDG inhibitor

Arb93A E242A with EDG inhibitor

Glycoside Hydrolase Family 93

2011-09-08T16:20:35Z

Annabelle Varrot: /* Three-dimensional structures */

Glycoside Hydrolase Family 93

2011-09-08T16:19:26Z

Annabelle Varrot: /* Substrate specificities */

Glycoside Hydrolase Family 93

2011-09-08T16:16:39Z

Annabelle Varrot: /* Kinetics and Mechanism */

Glycoside Hydrolase Family 93

2011-09-08T16:16:21Z

Annabelle Varrot: /* Substrate specificities */

Glycoside Hydrolase Family 93

2011-09-08T16:15:37Z

Annabelle Varrot: /* Three-dimensional structures */

Glycoside Hydrolase Family 93

2011-09-08T16:15:22Z

Annabelle Varrot: /* Catalytic Residues */

Glycoside Hydrolase Family 93

2011-09-08T16:15:03Z

Annabelle Varrot: /* Kinetics and Mechanism */

Glycoside Hydrolase Family 93

2011-09-08T16:11:26Z

Annabelle Varrot: /* References */

Glycoside Hydrolase Family 93

2011-09-08T16:08:13Z

Annabelle Varrot: /* Substrate specificities */

Glycoside Hydrolase Family 93

2011-09-08T16:07:44Z

Annabelle Varrot: /* Three-dimensional structures */

Glycoside Hydrolase Family 93

2011-09-08T16:06:01Z

Annabelle Varrot: /* Kinetics and Mechanism */

Glycoside Hydrolase Family 93

2011-09-08T15:46:39Z

Annabelle Varrot: /* References */

Glycoside Hydrolase Family 93

2011-09-08T15:28:17Z

Annabelle Varrot: /* References */

Glycoside Hydrolase Family 93

2011-09-08T15:21:38Z

Annabelle Varrot: /* References */

Glycoside Hydrolase Family 93

2011-09-08T15:17:59Z

Annabelle Varrot: /* Catalytic Residues */