Difference between revisions of "Glycoside Hydrolase Family 125"

Revision as of 10:29, 16 November 2012

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Author: ^^^Alisdair Boraston^^^
Responsible Curator: ^^^Alisdair Boraston^^^

Glycoside Hydrolase Family GH125
Clan	GH-L
Mechanism	inverting
Active site residues	known
CAZy DB link
http://www.cazy.org/GH125.html

Substrate specificities

The currently characterized family 125 glycoside hydrolyses, which include the examples from Streptococcus pneumoniae (SpGH125) and Clostridium perfringens (CpGH125), are α-mannosidases with specificity for α-1,6-linked non-reducing terminal mannose residues [1].

Kinetics and Mechanism

Kinetic characterization of 2,4-dinitrophenyl α-D-mannopyranoside hydrolysis by SpGH125 and Cp125 revealed that this is a poor substrate for these enzymes. Monitoring the hydrolysis of methyl 6-O-(α-D-mannopyranosyl)-β-D-mannopyranoside by sup>1H NMR spectroscopy revealed that CpGH125 and SpGH125 act with inversion of stereochemistry. The structural analysis of both enzymes reveal an arrangement of catalytic residues that is consistent with this mechanistic assignment [1].

Catalytic Residues

The structural analysis of CpGH125 suggests it uses aspartate 220 as a catalytic acid and glutamate 393 as catalytic base. The corresponding residues in SpGH125 are aspartame 218 and glutamate 391 [1].

Three-dimensional structures

The three dimensional structures of CpGH125 (3qt3, 3qt9, and 2nvp), SpGH125 (3qpf, 3qry, and 3qsp) are available and reveal both the (α/α)₆-fold of the family as well the details of inhibitor and substrate recognition. Though the proteins are uncharacterized, structures are also available for two GH125 enzymes from Bacteroides ovatus (3on6, and 3p2c) and one GH125 from Bacteroides thetaiotaomicron (2pov).

Family Firsts

First stereochemistry determination: ¹H NMR spectroscopy revealed that CpGH125 and SpGH125 act with inversion of stereochemistry [1].
First general base identification: CpGH125 and SpGH125 [1].
First general acid identification: CpGH125 and SpGH125 [1].
First 3-D structure: The first deposited structure was that of CpGH125 closely followed by the examples from Bacteroides sp. These structures were determined by the Structural Genomics Consortium. The first published structures were those of CpGH125 and SpGH125, which represented the first structures of these proteins in complex with carbohydrates [1].

References

Gregg KJ, Zandberg WF, Hehemann JH, Whitworth GE, Deng L, Vocadlo DJ, and Boraston AB. (2011). Analysis of a new family of widely distributed metal-independent alpha-mannosidases provides unique insight into the processing of N-linked glycans. J Biol Chem. 2011;286(17):15586-96. DOI:10.1074/jbc.M111.223172 | PubMed ID:21388958 [Gregg2011]

@@ Line 37: / Line 37: @@
 == Catalytic Residues ==
-The structural analysis of CpGH125 suggests it uses aspartate 220 as a catalytic acid and glutamate 393 as catalytic base. The corresponding residues in SpGH125 are aspartame 218 and glutamate 391.
+The structural analysis of CpGH125 suggests it uses aspartate 220 as a catalytic acid and glutamate 393 as catalytic base. The corresponding residues in SpGH125 are aspartame 218 and glutamate 391 <cite>Gregg2011</cite>.
 == Three-dimensional structures ==
-The three dimensional structures of CpGH125 ([{{PDBlink}}3qt3 3qt3], [{{PDBlink}}3qt9 3qt9], and [{{PDBlink}}2nvp 2nvp]), SpGH125 ([{{PDBlink}}3qpf 3qpf], [{{PDBlink}}3qry 3qry], and [{{PDBlink}}3qsp 3qsp]) are available and reveal both the (α/α)<sub>6</sub>-fold of the family as well the details of inhibitor and substrate recognition. Thought the proteins are uncharacterized structures are also available for two GH125 enzymes from BActeroides ovatus ([{{PDBlink}}3on6 3on6], and [{{PDBlink}}3p2c 3p2c]) and on GH125 from Bacteroides thetaiotaomicron ([{{PDBlink}}2pov 2pov]).
+The three dimensional structures of CpGH125 ([{{PDBlink}}3qt3 3qt3], [{{PDBlink}}3qt9 3qt9], and [{{PDBlink}}2nvp 2nvp]), SpGH125 ([{{PDBlink}}3qpf 3qpf], [{{PDBlink}}3qry 3qry], and [{{PDBlink}}3qsp 3qsp]) are available and reveal both the (α/α)<sub>6</sub>-fold of the family as well the details of inhibitor and substrate recognition. Though the proteins are uncharacterized, structures are also available for two GH125 enzymes from ''Bacteroides ovatus'' ([{{PDBlink}}3on6 3on6], and [{{PDBlink}}3p2c 3p2c]) and one GH125 from ''Bacteroides thetaiotaomicron'' ([{{PDBlink}}2pov 2pov]).
 == Family Firsts ==
 ;First stereochemistry determination: <sup>1</sup>H NMR spectroscopy revealed that CpGH125 and SpGH125 act with inversion of stereochemistry  <cite>Gregg2011</cite>.
-;First catalytic nucleophile identification: Cite some reference here, with a ''short'' (1-2 sentence) explanation <cite>Sinnott1990</cite>.
+;First [[general base]] identification: CpGH125 and SpGH125 <cite>Gregg2011</cite>.
-;First general acid/base residue identification: Cite some reference here, with a ''short'' (1-2 sentence) explanation <cite>He1999</cite>.
+;First [[general acid]] identification: CpGH125 and SpGH125 <cite>Gregg2011</cite>.
-;First 3-D structure: Cite some reference here, with a ''short'' (1-2 sentence) explanation <cite>StickWilliams</cite>.
+;First 3-D structure: The first deposited structure was that of CpGH125 closely followed by the examples from ''Bacteroides'' sp. These structures were determined by the Structural Genomics Consortium. The first published structures were those of CpGH125 and SpGH125, which represented the first structures of these proteins in complex with carbohydrates <cite>Gregg2011</cite>.
 == References ==