Glycoside Hydrolase Family 89 - Revision history

Harry Brumer: Text replacement - "User:Alisdair Boraston" to "User:Al Boraston"

2021-12-18T21:38:34Z

Text replacement - "User:Alisdair Boraston" to "User:Al Boraston"

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

2021-12-18T21:14:36Z

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

Elizabeth Ficko-Blean: /* Substrate specificities */

2020-05-25T18:50:41Z

Substrate specificities

Elizabeth Ficko-Blean: /* Three-dimensional structures */

2020-05-25T18:47:11Z

Three-dimensional structures

Elizabeth Ficko-Blean: /* Three-dimensional structures */

2020-05-25T18:44:43Z

Three-dimensional structures

Elizabeth Ficko-Blean: /* Three-dimensional structures */

2020-05-25T18:44:15Z

Three-dimensional structures

Elizabeth Ficko-Blean: /* Kinetics and Mechanism */

2020-05-25T18:42:41Z

Kinetics and Mechanism

Elizabeth Ficko-Blean: /* Substrate specificities */

2020-05-25T18:41:17Z

Substrate specificities

Elizabeth Ficko-Blean at 18:40, 25 May 2020

2020-05-25T18:40:09Z

Elizabeth Ficko-Blean at 18:37, 25 May 2020

2020-05-25T18:37:38Z

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 {{CuratorApproved}}
 * [[Author]]: [[User:Elizabeth Ficko-Blean|Elizabeth Ficko-Blean]]
-* [[Responsible Curator]]:  [[User:Alisdair Boraston|Alisdair Boraston]]
+* [[Responsible Curator]]:  [[User:Al Boraston|Alisdair Boraston]]
 ----

@@ Line 1: / Line 1: @@
 {{CuratorApproved}}
-* [[Author]]: ^^^Elizabeth Ficko-Blean^^^
+* [[Author]]: [[User:Elizabeth Ficko-Blean|Elizabeth Ficko-Blean]]
-* [[Responsible Curator]]:  ^^^Alisdair Boraston^^^
+* [[Responsible Curator]]:  [[User:Alisdair Boraston|Alisdair Boraston]]
 ----

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 == Substrate specificities ==
-Family 89 [[glycoside hydrolase]]s are α-N-acetylglucosaminidases <cite>Ficko-Blean-2008,Weber2000</cite>. CpGH89, produced by the animal pathogen ''Clostridium perfringens'', is active on the unusual α-D-GlcNAc-(1,4)-D-Galactose motif <cite>Fujita2011</cite> displayed on the gastric mucosal class III mucins <cite>Ishihara1996</cite>.  The human lysosomal enzyme, NAGLU, is involved in the degradation of heparan sulfate <cite>Yogalingham2001,Weber1999</cite>.   Mutations in this enzyme can cause a devastating disease called Sanfilippo syndrome type B which is also called mucopolysaccharidosis IIIB (MPS IIIB) <cite>Yogalingham2001,Weber1999</cite>.
+Family 89 [[glycoside hydrolase]]s are α-N-acetylglucosaminidases <cite>Ficko-Blean-2008,Weber2000</cite>. CpGH89, produced by the animal pathogen ''Clostridium perfringens'', is active on the unusual α-D-GlcNAc-(1,4)-D-Galactose motif <cite>Fujita2011</cite> displayed on the gastric mucosal class III mucins <cite>Ishihara1996</cite>.  The human lysosomal enzyme, NAGLU, is involved in the degradation of heparan sulfate <cite>Yogalingham2001,Weber1999</cite>.   Mutations in this enzyme can cause a devastating lysosomal storage disorder called Sanfilippo syndrome type B which is also called mucopolysaccharidosis IIIB (MPS IIIB) <cite>Yogalingham2001,Weber1999</cite>.
 == Kinetics and Mechanism ==

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 The three dimensional structure was first described for CpGH89,  see PDB entries [{{PDBlink}}2vc9 2vc9], [{{PDBlink}}2vca 2vca], [{{PDBlink}}2vcb 2vcb],[{{PDBlink}}2vcc 2vcc] <cite>Ficko-Blean-2008</cite> followed by the structure of a CpGH89 double catalytic residue mutant in complex with the class III mucosal disaccharide α-D-GlcNAc-(1,4)-D-Galactose, [{{PDBlink}}4a4a 4a4a] (Figure 1) <cite>Ficko-Blean-Michaelis-complex2012</cite>.   The structure of the human enzyme NAGLU, [{{PDBlink}}4xwh 4xwh], was released in 2019 <cite>Birrane2019</cite>.
-CpGH89 is a multi-modular protein and quite large (2095 amino acids) and contains six modules with sequence similarity to the family 32 carbohydrate-binding modules ([[CBM32]]s) <cite>Ficko-Blean-CBMs2012</cite>. Only residues 26-916 were crystallized <cite>Ficko-Blean-2008</cite>.  The N-terminal domain (residues 26-155) forms a β-sandwich fold and is one of the [[CBM32]]-like domains.  This module is tightly packed against the rest of the protein through a number of hydrophobic and hydrogen bonding interactions and is not predicted to be functional in carbohydrate-binding <cite>Ficko-Blean-CBMs2012</cite>. The catalytic region is comprised of a small mixed α/β domain (residues 170-280), a decorated (α/β)<sub>8</sub> core (residues 280-620), and an all α-helical domain (residues 621-916) <cite>Ficko-Blean-2008</cite>.  The active site is sock-shaped to accommodate the bend in the class III mucosal α-D-GlcNAc-(1,4)-D-Galactose motif caused by the alpha glycosidic linkage (Figure 1) <cite>Ficko-Blean-Michaelis-complex2012,Ficko-Blean-2008</cite>. The mutations causing MPS IIIB were mapped onto the bacterial homologue, demonstrating that the mutations are mainly structural in nature <cite>Ficko-Blean-2008</cite>.
+CpGH89 is a multi-modular protein and quite large (2095 amino acids) and contains six modules with sequence similarity to the family 32 carbohydrate-binding modules ([[CBM32]]s) <cite>Ficko-Blean-CBMs2012</cite>. To obtain the CpGH89 catalytic module structure, only residues 26-916 were crystallized <cite>Ficko-Blean-2008</cite>.  The N-terminal domain (residues 26-155) forms a β-sandwich fold and is one of the [[CBM32]]-like domains.  This module is tightly packed against the rest of the protein through a number of hydrophobic and hydrogen bonding interactions and is not predicted to be functional in carbohydrate-binding <cite>Ficko-Blean-CBMs2012</cite>. The catalytic region is comprised of a small mixed α/β domain (residues 170-280), a decorated (α/β)<sub>8</sub> core (residues 280-620), and an all α-helical domain (residues 621-916) <cite>Ficko-Blean-2008</cite>.  The active site is sock-shaped to accommodate the bend in the class III mucosal α-D-GlcNAc-(1,4)-D-Galactose motif caused by the alpha glycosidic linkage (Figure 1) <cite>Ficko-Blean-Michaelis-complex2012,Ficko-Blean-2008</cite>. The mutations causing MPS IIIB were mapped onto the bacterial homologue, demonstrating that the mutations are mainly structural in nature <cite>Ficko-Blean-2008</cite>.
 NAGLU has only 28.2% sequence identity with CpGH89 and lacks the [[CBM32]]-like domain.  Otherwise the tertiary structures of CpGH89 and NAGLU are similar <cite>Birrane2019</cite>. The predicted catalytic glutamates, E316 and E446, are present in NAGLU <cite>Birrane2019</cite>.  NAGLU has six potential N-glycosylation sites and appears to be N-glycosylated <cite>Birrane2019</cite>. The recombinant enzyme was produced as a trimer in solution though the physiological relevance of the trimer is unknown <cite>Birrane2019</cite>. In comparison, CpGH89 crystallized as a monomer in the asymmetric unit <cite>Ficko-Blean-2008</cite>. The substrate binding pocket of NAGLU is more open when compared to the sock-shaped active site of CpGH89 <cite>Ficko-Blean-2008,Birrane2019</cite>. The mutations causing MPS IIIB were also mapped onto NAGLU, confirming that the mutations are mainly structural in nature <cite>Birrane2019</cite>.

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 == Three-dimensional structures ==
-The three dimensional structure was first described for CpGH89,  see PDB entries [{{PDBlink}}2vc9 2vc9], [{{PDBlink}}2vca 2vca], [{{PDBlink}}2vcb 2vcb],[{{PDBlink}}2vcc 2vcc] <cite>Ficko-Blean-2008</cite> followed by the structure of a CpGH89 double catalytic residue mutant in complex with the class III mucosal disaccharide α-D-GlcNAc-(1,4)-D-Galactose [{{PDBlink}}4a4a 4a4a] (Figure 1) <cite>Ficko-Blean-Michaelis-complex2012</cite>.   The structure of the human enzyme NAGLU, [{{PDBlink}}4xwh 4xwh], was released in 2019 <cite>Birrane2019</cite>.
+The three dimensional structure was first described for CpGH89,  see PDB entries [{{PDBlink}}2vc9 2vc9], [{{PDBlink}}2vca 2vca], [{{PDBlink}}2vcb 2vcb],[{{PDBlink}}2vcc 2vcc] <cite>Ficko-Blean-2008</cite> followed by the structure of a CpGH89 double catalytic residue mutant in complex with the class III mucosal disaccharide α-D-GlcNAc-(1,4)-D-Galactose, [{{PDBlink}}4a4a 4a4a] (Figure 1) <cite>Ficko-Blean-Michaelis-complex2012</cite>.   The structure of the human enzyme NAGLU, [{{PDBlink}}4xwh 4xwh], was released in 2019 <cite>Birrane2019</cite>.
 CpGH89 is a multi-modular protein and quite large (2095 amino acids) and contains six modules with sequence similarity to the family 32 carbohydrate-binding modules ([[CBM32]]s) <cite>Ficko-Blean-CBMs2012</cite>. Only residues 26-916 were crystallized <cite>Ficko-Blean-2008</cite>.  The N-terminal domain (residues 26-155) forms a β-sandwich fold and is one of the [[CBM32]]-like domains.  This module is tightly packed against the rest of the protein through a number of hydrophobic and hydrogen bonding interactions and is not predicted to be functional in carbohydrate-binding <cite>Ficko-Blean-CBMs2012</cite>. The catalytic region is comprised of a small mixed α/β domain (residues 170-280), a decorated (α/β)<sub>8</sub> core (residues 280-620), and an all α-helical domain (residues 621-916) <cite>Ficko-Blean-2008</cite>.  The active site is sock-shaped to accommodate the bend in the class III mucosal α-D-GlcNAc-(1,4)-D-Galactose motif caused by the alpha glycosidic linkage (Figure 1) <cite>Ficko-Blean-Michaelis-complex2012,Ficko-Blean-2008</cite>. The mutations causing MPS IIIB were mapped onto the bacterial homologue, demonstrating that the mutations are mainly structural in nature <cite>Ficko-Blean-2008</cite>.

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 == Kinetics and Mechanism ==
-Mechanistic data is available on CpGH89, a family 89 glycoside hydrolase produced by ''Clostridium perfringens''.  CpGH89 uses a [[classical Koshland retaining mechanism]] to hydrolyze the glycosidic bond. This results in hydrolysis with a net retention of stereochemistry at the anomeric carbon <cite>Ficko-Blean-2008</cite>.
+Mechanistic data is available on CpGH89, a family 89 glycoside hydrolase produced by ''Clostridium perfringens''.  CpGH89 uses a [[classical Koshland retaining mechanism]] to hydrolyze the glycosidic bond <cite>Ficko-Blean-2008</cite>. This results in hydrolysis with a net retention of stereochemistry at the anomeric carbon <cite>Ficko-Blean-2008</cite>.
 == Catalytic Residues ==

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 == References ==
 <biblio>
-#[Ficko-Blean-2008] pmid=18443291
+#Ficko-Blean-2008 pmid=18443291
-#[Weber2000] pmid=11237686
+#Weber2000 pmid=11237686
-#[Yogalingham2001] pmid=11668611
+#Yogalingham2001 pmid=11668611
-#[Weber1999] pmid=10094189
+#Weber1999 pmid=10094189
-#[Birrane2019] pmid=30802506
+#Birrane2019 pmid=30802506
-#[Ficko-Blean-Michaelis-complex2012] pmid=22090394
+#Ficko-Blean-Michaelis-complex2012 pmid=22090394
-#[Fujita2011] pmid=21177247
+#Fujita2011 pmid=21177247
-#[Ishihara1996] pmid=8809027
+#Ishihara1996 pmid=8809027
-#[Ficko-Blean-CBMs2012] pmid=22479408
+#Ficko-Blean-CBMs2012 pmid=22479408
 </biblio>
 [[Category:Glycoside Hydrolase Families|GH089]]