Carbohydrate Esterase Family 9 - Revision history

Harry Brumer: Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

2021-12-18T21:17:26Z

Text replacement - "\^\^\^(.*)\^\^\^" to "$1"

Harry Brumer: adjusted in-text citations

2020-06-10T16:24:44Z

adjusted in-text citations

Michael Suits at 20:16, 28 February 2019

2019-02-28T20:16:25Z

Alex Anderson at 17:21, 28 February 2019

2019-02-28T17:21:49Z

Harry Brumer: fixed Family Firsts list formatting

2018-10-18T00:41:01Z

fixed Family Firsts list formatting

Harry Brumer at 00:31, 18 October 2018

2018-10-18T00:31:29Z

Alex Anderson at 17:51, 27 August 2018

2018-08-27T17:51:01Z

Alex Anderson at 17:14, 27 August 2018

2018-08-27T17:14:18Z

Harry Brumer: Created page with " {{UnderConstruct..."

2018-05-30T11:48:09Z

Created page with " {{UnderConstruct..."

New page

{{UnderConstruction}}
* [[Author]]: ^^^Alex Anderson^^^
* [[Responsible Curator]]: ^^^Michael Suits^^^
----


<div style="float:right">
{| {{Prettytable}}
|-
|{{Hl2}} colspan="2" align="center" |'''Carbohydrate Esterase Family 9'''
|-
|'''Clan'''
|GH-x
|-
|'''Mechanism'''
|retaining/inverting
|-
|'''Active site residues'''
|known/not known
|-
|{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''
|-
| colspan="2" |{{CAZyDBlink}}CE9.html
|}
</div>


== Substrate specificities ==
Content is to be added here.

Authors may get an idea of what to put in each field from ''Curator Approved'' [[Glycoside Hydrolase Families]]. ''(TIP: Right click with your mouse and open this link in a new browser window...)''

In the meantime, please see these references for an essential introduction to the CAZy classification system: <cite>DaviesSinnott2008 Cantarel2009</cite>.

== Kinetics and Mechanism ==
Content is to be added here.

== Catalytic Residues ==
Content is to be added here.

== Three-dimensional structures ==
Content is to be added here.

== Family Firsts ==
;First stereochemistry determination: Content is to be added here.
;First catalytic nucleophile identification: Content is to be added here.
;First general acid/base residue identification: Content is to be added here.
;First 3-D structure: Content is to be added here.

== References ==
<biblio>
#Cantarel2009 pmid=18838391
#DaviesSinnott2008 Davies, G.J. and Sinnott, M.L. (2008) Sorting the diverse: the sequence-based classifications of carbohydrate-active enzymes. ''The Biochemist'', vol. 30, no. 4., pp. 26-32. [http://www.biochemist.org/bio/03004/0026/030040026.pdf Download PDF version].
</biblio>

[[Category:Carbohydrate Esterase Families|CE009]]

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 == Substrate specificities ==
-CE family 9 esterases catalyze the deacetylation of N-acetylglucosamine-6-phosphate to glucosamine-6-phosphate. This reaction has been demonstrated to be important for both amino sugar metabolism and peptidoglycan cell wall recycling in bacteria <cite>#Park2001</cite>. Experimental substrate specificity profiles for two CE9 enzymes demonstrated that they are active on other structurally similar amino sugar phosphates, such as N-acetyl- galactosamine-6-phosphate and N-acetyl-mannosamine-6-phosphate, although their reported affinities are 40-fold and 6-fold lower, respectively <cite>#Ahangar2018</cite>.
+CE family 9 esterases catalyze the deacetylation of N-acetylglucosamine-6-phosphate to glucosamine-6-phosphate. This reaction has been demonstrated to be important for both amino sugar metabolism and peptidoglycan cell wall recycling in bacteria <cite>Park2001</cite>. Experimental substrate specificity profiles for two CE9 enzymes demonstrated that they are active on other structurally similar amino sugar phosphates, such as N-acetyl- galactosamine-6-phosphate and N-acetyl-mannosamine-6-phosphate, although their reported affinities are 40-fold and 6-fold lower, respectively <cite>Ahangar2018</cite>.
 == Kinetics and Mechanism ==
-Removal of the acetate group by CE9 enzymes is proposed to be carried out by nucleophilic attack of the acetate carbon by a metal-bound hydroxide ion <cite>#Vincent2004</cite>. A proton is donated to the amine leaving group by a catalytic acid residue, and the tetrahedral transition state is stabilized either by the interaction of a second metal ion with the polarized carbonyl oxygen <cite>#Vincent2004</cite>, or by a catalytic base residue where a second metal ion is absent from the active site, although the latter has not been experimentally demonstrated.
+Removal of the acetate group by CE9 enzymes is proposed to be carried out by nucleophilic attack of the acetate carbon by a metal-bound hydroxide ion <cite>Vincent2004</cite>. A proton is donated to the amine leaving group by a catalytic acid residue, and the tetrahedral transition state is stabilized either by the interaction of a second metal ion with the polarized carbonyl oxygen <cite>Vincent2004</cite>, or by a catalytic base residue where a second metal ion is absent from the active site, although the latter has not been experimentally demonstrated.
 == Catalytic Residues ==
-The precise mechanism of catalysis has yet to be elucidated for CE9, although several conserved features in the active sites of resolved CE9 members suggest they play an important role in their function. In ''Bacillus subtilis'' NagA, ''Thermotoga maritima'' NagA, and ''Mycobacterium smegmatis'' NagA, four histidine residues are responsible for coordination of the metal cofactor(s), along with a glutamate in ''B. subtilis'' and ''T. maritima'', and an aspartic acid in ''M. smegmatis'' <cite>#Vincent2004,#Osipiuk2002,#Ferreira2006</cite>. The ''Escherichia coli'' NagA appears to have a glutamine, gluatamate, asparagine and an aspartate as the coordination enviroment, although this structure crystallized as the apoenzyme, and so this configuration is uncertain <cite>#Ferreira2006</cite>. In all structures, a strictly conserved aspartic acid residue is then thought to serve as a base to activate a water molecule, and then as an acid to protonate the leaving amine <cite>#Vincent2004</cite>.
+The precise mechanism of catalysis has yet to be elucidated for CE9, although several conserved features in the active sites of resolved CE9 members suggest they play an important role in their function. In ''Bacillus subtilis'' NagA, ''Thermotoga maritima'' NagA, and ''Mycobacterium smegmatis'' NagA, four histidine residues are responsible for coordination of the metal cofactor(s), along with a glutamate in ''B. subtilis'' and ''T. maritima'', and an aspartic acid in ''M. smegmatis'' <cite>Vincent2004,Osipiuk2002,Ferreira2006</cite>. The ''Escherichia coli'' NagA appears to have a glutamine, gluatamate, asparagine and an aspartate as the coordination enviroment, although this structure crystallized as the apoenzyme, and so this configuration is uncertain <cite>Ferreira2006</cite>. In all structures, a strictly conserved aspartic acid residue is then thought to serve as a base to activate a water molecule, and then as an acid to protonate the leaving amine <cite>Vincent2004</cite>.
 == Three-dimensional structures ==
-The resolved structures of CE9 enzymes demonstrate variability in their organization and metal binding. For example, ''Vibrio cholerae'' NagA and ''B. subtilis'' NagA form dimers in their biologically relevant assemblies <cite>#Osipiuk2002, #Vincent2004</cite>, while ''E. coli'' NagA forms a tetramer <cite>#Ferreira2006</cite>. Additionally, these same enzymes appear to contain a Ni<sup>2+</sup> ion <cite>#Osipiuk2002</cite>, two Fe<sup>2+</sup> ions <cite>#Vincent2004</cite>, and a Zn<sup>2+</sup> ion <cite>#Ferreira2006</cite> in their active sites, respectively. All resolved CE9 enzymes contain a distorted (β/α)<sub>8</sub> fold containing the active site, and a small β-sheet domain comprising residues from both the N- and C-termini.
+The resolved structures of CE9 enzymes demonstrate variability in their organization and metal binding. For example, ''Vibrio cholerae'' NagA and ''B. subtilis'' NagA form dimers in their biologically relevant assemblies <cite>Osipiuk2002, Vincent2004</cite>, while ''E. coli'' NagA forms a tetramer <cite>Ferreira2006</cite>. Additionally, these same enzymes appear to contain a Ni<sup>2+</sup> ion <cite>Osipiuk2002</cite>, two Fe<sup>2+</sup> ions <cite>Vincent2004</cite>, and a Zn<sup>2+</sup> ion <cite>Ferreira2006</cite> in their active sites, respectively. All resolved CE9 enzymes contain a distorted (β/α)<sub>8</sub> fold containing the active site, and a small β-sheet domain comprising residues from both the N- and C-termini.
 == Family Firsts ==
-;First characterized: The ''E. coli'' N-acetylglucosamine-6-phosphate deacetylase NagA was the first CE9 enzyme to have its activity demonstrated <cite>#White1967</cite>.
+;First characterized: The ''E. coli'' N-acetylglucosamine-6-phosphate deacetylase NagA was the first CE9 enzyme to have its activity demonstrated <cite>White1967</cite>.
-;First 3-D structure: The first structure of a CE9 enzyme published was the ''B. subtilis'' NagA, containing a two-Fe<sup>2+</sup> catalytic center <cite>#Vincent2004</cite>.
+;First 3-D structure: The first structure of a CE9 enzyme published was the ''B. subtilis'' NagA, containing a two-Fe<sup>2+</sup> catalytic center <cite>Vincent2004</cite>.
-;First mechanistic insight: The structure of the ''B. subtilis'' NagA enzyme was reported with a bound N-acetylglucosamine-6-phosphate molecule and provided evidence for the proposed metal-dependent catalytic mechanism <cite>#Vincent2004</cite>.
+;First mechanistic insight: The structure of the ''B. subtilis'' NagA enzyme was reported with a bound N-acetylglucosamine-6-phosphate molecule and provided evidence for the proposed metal-dependent catalytic mechanism <cite>Vincent2004</cite>.
 == References ==

@@ Line 41: / Line 41: @@
 == Family Firsts ==
-;First characterized
+;First characterized: The ''E. coli'' N-acetylglucosamine-6-phosphate deacetylase NagA was the first CE9 enzyme to have its activity demonstrated <cite>#White1967</cite>.
-The ''E. coli'' N-acetylglucosamine-6-phosphate deacetylase NagA was the first CE9 enzyme to have its activity demonstrated <cite>#White1967</cite>.
+;First 3-D structure: The first structure of a CE9 enzyme published was the ''B. subtilis'' NagA, containing a two-Fe<sup>2+</sup> catalytic center <cite>#Vincent2004</cite>.
-;First 3-D structure
+;First mechanistic insight: The structure of the ''B. subtilis'' NagA enzyme was reported with a bound N-acetylglucosamine-6-phosphate molecule and provided evidence for the proposed metal-dependent catalytic mechanism <cite>#Vincent2004</cite>.
 The first structure of a CE9 enzyme published was the ''B. subtilis'' NagA, containing a two-Fe<sup>2+</sup> catalytic center <cite>#Vincent2004</cite>.
 == References ==
 <biblio>

@@ Line 50: / Line 50: @@
 <biblio>
 #Park2001 pmid=11395446
+#Osipiuk2002 PDB entry [{{PDBlink}}3EGJ 3egj], unpublished.
 #Vincent2004 pmid=14557261
 #Ferreira2006 pmid=16630633
 #Ahangar2018 pmid=29728457
 #White1967 pmid=4861885
 </biblio>
 [[Category:Carbohydrate Esterase Families|CE009]]

@@ Line 57: / Line 57: @@
 #Ferreira2006 pmid=16630633
-#Ahangar2018 pmid= 29728457
+#Ahangar2018 pmid=29728457
 #White1967 pmid=4861885

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 <!-- RESPONSIBLE CURATORS: Please replace the {{UnderConstruction}} tag below with {{CuratorApproved}} when the page is ready for wider public consumption -->
 {{CuratorApproved}}
-* [[Author]]: ^^^Alex Anderson^^^
+* [[Author]]: [[User:Alex Anderson|Alex Anderson]]
-* [[Responsible Curator]]:  ^^^Michael Suits^^^
+* [[Responsible Curator]]:  [[User:Michael Suits|Michael Suits]]
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 |{{Hl2}} colspan="2" align="center" |'''Carbohydrate Esterase Family 9'''
 |-
-|'''Clan'''
+|'''Acid/alcohol sugar substrate'''
-|GH-x
+|Alcohol
 |-
-|'''Mechanism'''
+|'''Metal-dependent'''
-|retaining/inverting
+|Yes
 |-
 |'''Active site residues'''
-|not known
+|Known
 |-
 |{{Hl2}} colspan="2" align="center" |'''CAZy DB link'''