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| Enzyme Name | | Swiss-prot | KEGG |
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| Q16775 |
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| Protein name | Hydroxyacylglutathione hydrolase | hydroxyacylglutathione hydrolaseglyoxalase IIS-2-hydroxylacylglutathione hydrolasehydroxyacylglutathione hydrolaseacetoacetylglutathione hydrolase |
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| Synonyms | EC 3.1.2.6Glyoxalase IIGlx II |
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| KEGG pathways | | MAP code | Pathways |
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| MAP00620 | Pyruvate metabolism |
| Swiss-prot:Accession Number | Q16775 |
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| Entry name | GLO2_HUMAN |
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| Activity | S-(2-hydroxyacyl)glutathione + H(2)O = glutathione + a 2-hydroxy carboxylate. |
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| Subunit | Monomer. |
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| Subcellular location |
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| Cofactor | Binds 2 zinc ions per subunit. |
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| Cofactors | Substrates | Products | intermediates |
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| KEGG-id | C00038 | C03899 | C00001 | C00051 | C02929 |
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| Compound | Zinc | S-(2-Hydroxyacyl)glutathione | H2O | Glutathione | 2-Hydroxycarboxylate |
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| Type | heavy metal | amino acids,carbohydrate,carboxyl group,peptide/protein,sulfide group | H2O | amino acids,carboxyl group,peptide/protein,sulfhydryl group | carbohydrate,carboxyl group |
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| 1qh3A |  | Bound:2x_ZN | Unbound |
| Unbound | Unbound | Analogue:CAC |
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| 1qh3B | | Bound:2x_ZN | Unbound |
| Unbound | Unbound | Analogue:CAC |
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| 1qh5A | | Bound:2x_ZN | Unbound |
| Bound:GTT | Unbound | Unbound |
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| 1qh5B | | Bound:2x_ZN | Analogue:GBP |
| Unbound | Unbound | Unbound |
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| References for Catalytic Mechanism | | References | Sections | No. of steps in catalysis |
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| [1] | Fig.8, p.1074-1076 | 2 |
| references | | [1] |
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| Comments | X-ray crystallography (1.9/1.45 Angstroms) |
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| PubMed ID | 10508780 |
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| Journal | Structure Fold Des |
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| Year | 1999 |
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| Volume | 7 |
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| Pages | 1067-78 |
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| Authors | Cameron AD, Ridderstrom M, Olin B, Mannervik B |
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| Title | Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue. |
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| Related PDB | 1qh3,1qh5 |
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| Related Swiss-prot | Q16775 |
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| [2] |
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| Comments | Active site mutation |
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| PubMed ID | 11018726 |
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| Journal | Biochim Biophys Acta |
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| Year | 2000 |
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| Volume | 1481 |
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| Pages | 344-8 |
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| Authors | Ridderstrom M, Jemth P, Cameron AD, Mannervik B |
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| Title | The active-site residue tyr-175 in human glyoxalase II contributes to binding of glutathione derivatives. |
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| 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].
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| created | updated |
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| 2002-09-06 | 2009-02-26 |
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