EzCatDB: S00431
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DB codeS00431
RLCP classification1.14.10105.1251 : Hydrolysis
CATH domainDomain 13.60.15.10 : Metallo-beta-lactamase; Chain ACatalytic domain
E.C.3.1.2.6
CSA1qh5
MACiEM0157

CATH domainRelated DB codes (homologues)
3.60.15.10 : Metallo-beta-lactamase; Chain AS00515,S00432

Enzyme Name
UniProtKBKEGG

Q16775
Protein nameHydroxyacylglutathione hydrolasehydroxyacylglutathione hydrolase
glyoxalase II
S-2-hydroxylacylglutathione hydrolase
hydroxyacylglutathione hydrolase
acetoacetylglutathione hydrolase
SynonymsEC 3.1.2.6
Glyoxalase II
Glx II
RefSeqNP_001035517.1 (Protein)
NM_001040427.1 (DNA/RNA sequence)
NP_005317.2 (Protein)
NM_005326.4 (DNA/RNA sequence)
PfamPF00753 (Lactamase_B)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00620Pyruvate metabolism

UniProtKB:Accession NumberQ16775
Entry nameGLO2_HUMAN
ActivityS-(2-hydroxyacyl)glutathione + H(2)O = glutathione + a 2-hydroxy carboxylate.
SubunitMonomer.
Subcellular location
CofactorBinds 2 zinc ions per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00038C03899C00001C00051C02929
CompoundZincS-(2-Hydroxyacyl)glutathioneH2OGlutathione2-Hydroxycarboxylate
Typeheavy metalamino acids,carbohydrate,carboxyl group,peptide/protein,sulfide groupH2Oamino acids,carboxyl group,peptide/protein,sulfhydryl groupcarbohydrate,carboxyl group
ChEBI29105

15377
16856


PubChem32051

962
22247451
25246407
124886


              
1qh3ABound:2x_ZNUnbound UnboundUnboundAnalogue:CAC
1qh3BBound:2x_ZNUnbound UnboundUnboundAnalogue:CAC
1qh5ABound:2x_ZNUnbound Bound:GTTUnboundUnbound
1qh5BBound:2x_ZNAnalogue:GBP UnboundUnboundUnbound

Active-site residues
resource
Swiss-prot & PDB
pdbCofactor-binding residues
         
1qh3AHIS 54;HIS 56;HIS 110(Zinc-1 binding);ASP 134(both zinc binding);ASP 58;HIS 59;ASP 134;HIS 173(Zinc-2 binding)
1qh3BHIS 54;HIS 56;HIS 110(Zinc-1 binding);ASP 134(both zinc binding);ASP 58;HIS 59;ASP 134;HIS 173(Zinc-2 binding)
1qh5AHIS 54;HIS 56;HIS 110(Zinc-1 binding);ASP 134(both zinc binding);ASP 58;HIS 59;ASP 134;HIS 173(Zinc-2 binding)
1qh5BHIS 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
ReferencesSectionsNo. of steps in catalysis
[1]Fig.8, p.1074-10762

references
[1]
CommentsX-ray crystallography (1.9/1.45 Angstroms)
PubMed ID10508780
JournalStructure Fold Des
Year1999
Volume7
Pages1067-78
AuthorsCameron AD, Ridderstrom M, Olin B, Mannervik B
TitleCrystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue.
Related PDB1qh3,1qh5
Related UniProtKBQ16775
[2]
CommentsActive site mutation
PubMed ID11018726
JournalBiochim Biophys Acta
Year2000
Volume1481
Pages344-8
AuthorsRidderstrom M, Jemth P, Cameron AD, Mannervik B
TitleThe active-site residue tyr-175 in human glyoxalase II contributes to binding of glutathione derivatives.

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].

createdupdated
2002-09-062009-02-26


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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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