DB code: S00431

RLCP classification 1.14.10105.1251 : Hydrolysis
CATH domain 3.60.15.10 : Metallo-beta-lactamase; Chain A Catalytic domain
E.C. 3.1.2.6
CSA 1qh5
M-CSA 1qh5
MACiE M0157

CATH domain Related DB codes (homologues)
3.60.15.10 : Metallo-beta-lactamase; Chain A S00515 S00432

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q16775 Hydroxyacylglutathione hydrolase
EC 3.1.2.6
Glyoxalase II
Glx II
NP_001035517.1 (Protein)
NM_001040427.1 (DNA/RNA sequence)
NP_005317.2 (Protein)
NM_005326.4 (DNA/RNA sequence)
PF00753 (Lactamase_B)
[Graphical View]

KEGG enzyme name
hydroxyacylglutathione hydrolase
glyoxalase II
S-2-hydroxylacylglutathione hydrolase
hydroxyacylglutathione hydrolase
acetoacetylglutathione hydrolase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q16775 GLO2_HUMAN S-(2-hydroxyacyl)glutathione + H(2)O = glutathione + a 2-hydroxy carboxylate. Monomer. Binds 2 zinc ions per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP00620 Pyruvate metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00038 C03899 C00001 C00051 C02929
E.C.
Compound Zinc S-(2-Hydroxyacyl)glutathione H2O Glutathione 2-Hydroxycarboxylate
Type heavy metal amino acids,carbohydrate,carboxyl group,peptide/protein,sulfide group H2O amino acids,carboxyl group,peptide/protein,sulfhydryl group carbohydrate,carboxyl group
ChEBI 29105
15377
16856
PubChem 32051
22247451
962
124886
25246407
1qh3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Unbound Unbound Analogue:CAC
1qh3B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Unbound Unbound Analogue:CAC
1qh5A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Unbound Bound:GTT Unbound Unbound
1qh5B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_ZN Analogue:GBP Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot & PDB

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1qh3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 54;HIS 56;HIS 110(Zinc-1 binding);ASP 134(both zinc binding);ASP 58;HIS 59;ASP 134;HIS 173(Zinc-2 binding)
1qh3B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 54;HIS 56;HIS 110(Zinc-1 binding);ASP 134(both zinc binding);ASP 58;HIS 59;ASP 134;HIS 173(Zinc-2 binding)
1qh5A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 54;HIS 56;HIS 110(Zinc-1 binding);ASP 134(both zinc binding);ASP 58;HIS 59;ASP 134;HIS 173(Zinc-2 binding)
1qh5B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 54;HIS 56;HIS 110(Zinc-1 binding);ASP 134(both zinc binding);ASP 58;HIS 59;ASP 134;HIS 173(Zinc-2 binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Fig.8, p.1074-1076 2

References
[1]
Resource
Comments X-ray crystallography (1.9/1.45 Angstroms)
Medline ID
PubMed ID 10508780
Journal Structure Fold Des
Year 1999
Volume 7
Pages 1067-78
Authors Cameron AD, Ridderstrom M, Olin B, Mannervik B
Title Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue.
Related PDB 1qh3 1qh5
Related UniProtKB Q16775
[2]
Resource
Comments Active site mutation
Medline ID
PubMed ID 11018726
Journal Biochim Biophys Acta
Year 2000
Volume 1481
Pages 344-8
Authors Ridderstrom M, Jemth P, Cameron AD, Mannervik B
Title The active-site residue tyr-175 in human glyoxalase II contributes to binding of glutathione derivatives.
Related PDB
Related UniProtKB

Comments
According to the literature [1], the reaction is thought to involve a nucleophilic attack on the C1 atom of the substrate. Presumably, the interaction of the water molecule with the two zinc ions, would lower its pKa sufficiently for it to exist in the form of a hydroxide and alleviate the need for a base to abstract a proton. Asp58 will help orient the hydroxide for attack and modify its pKa. The nucleophilic attack on C1 atom of the substrate would presumably result in a negatively charged tetrahedral intermediate. Putative transition-state structure with both oxygen atoms interacting with zinc-1. To complete the interaction, the C1-S bond must be broken, the glutathione protonated and the products must diffuse from the active site to be replaced by water molecules. Without further information, it is difficult to describe how it occurs. However, the sulphur atoms of the substrate analogue or product, glutathione are close enough from zinc-2. Thus, one possibility is that the zinc ion will stabilise a thiolate ion formed upon bond cleavage [1].

Created Updated
2002-09-06 2009-02-26