1qh5: Difference between revisions
New page: left|200px<br /> <applet load="1qh5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qh5, resolution 1.45Å" /> '''HUMAN GLYOXALASE II... |
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[[Image:1qh5.gif|left|200px]]<br /> | [[Image:1qh5.gif|left|200px]]<br /><applet load="1qh5" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1qh5, resolution 1.45Å" /> | caption="1qh5, resolution 1.45Å" /> | ||
'''HUMAN GLYOXALASE II WITH S-(N-HYDROXY-N-BROMOPHENYLCARBAMOYL)GLUTATHIONE'''<br /> | '''HUMAN GLYOXALASE II WITH S-(N-HYDROXY-N-BROMOPHENYLCARBAMOYL)GLUTATHIONE'''<br /> | ||
==Overview== | ==Overview== | ||
BACKGROUND: Glyoxalase II, the second of two enzymes in the glyoxalase | BACKGROUND: Glyoxalase II, the second of two enzymes in the glyoxalase system, is a thiolesterase that catalyses the hydrolysis of S-D-lactoylglutathione to form glutathione and D-lactic acid. RESULTS: The structure of human glyoxalase II was solved initially by single isomorphous replacement with anomalous scattering and refined at a resolution of 1.9 A. The enzyme consists of two domains. The first domain folds into a four-layered beta sandwich, similar to that seen in the metallo-beta-lactamases. The second domain is predominantly alpha-helical. The active site contains a binuclear zinc-binding site and a substrate-binding site extending over the domain interface. The model contains acetate and cacodylate in the active site. A second complex was derived from crystals soaked in a solution containing the slow substrate, S-(N-hydroxy-N-bromophenylcarbamoyl)glutathione. This complex was refined at a resolution of 1.45 A. It contains the added ligand in one molecule of the asymmetric unit and glutathione in the other. CONCLUSIONS: The arrangement of ligands around the zinc ions includes a water molecule, presumably in the form of a hydroxide ion, coordinated to both metal ions. This hydroxide ion is situated 2.9 A from the carbonyl carbon of the substrate in such a position that it could act as the nucleophile during catalysis. The reaction mechanism may also have implications for the action of metallo-beta-lactamases. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1QH5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, GTT and GBP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Hydroxyacylglutathione_hydrolase Hydroxyacylglutathione hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.6 3.1.2.6] Full crystallographic information is available from [http:// | 1QH5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=GTT:'>GTT</scene> and <scene name='pdbligand=GBP:'>GBP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Hydroxyacylglutathione_hydrolase Hydroxyacylglutathione hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.6 3.1.2.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QH5 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Hydroxyacylglutathione hydrolase]] | [[Category: Hydroxyacylglutathione hydrolase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Cameron, A | [[Category: Cameron, A D.]] | ||
[[Category: Mannervik, B.]] | [[Category: Mannervik, B.]] | ||
[[Category: Olin, B.]] | [[Category: Olin, B.]] | ||
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[[Category: metallo-hydrolase]] | [[Category: metallo-hydrolase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:39:28 2008'' | ||
Revision as of 15:39, 21 February 2008
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HUMAN GLYOXALASE II WITH S-(N-HYDROXY-N-BROMOPHENYLCARBAMOYL)GLUTATHIONE
OverviewOverview
BACKGROUND: Glyoxalase II, the second of two enzymes in the glyoxalase system, is a thiolesterase that catalyses the hydrolysis of S-D-lactoylglutathione to form glutathione and D-lactic acid. RESULTS: The structure of human glyoxalase II was solved initially by single isomorphous replacement with anomalous scattering and refined at a resolution of 1.9 A. The enzyme consists of two domains. The first domain folds into a four-layered beta sandwich, similar to that seen in the metallo-beta-lactamases. The second domain is predominantly alpha-helical. The active site contains a binuclear zinc-binding site and a substrate-binding site extending over the domain interface. The model contains acetate and cacodylate in the active site. A second complex was derived from crystals soaked in a solution containing the slow substrate, S-(N-hydroxy-N-bromophenylcarbamoyl)glutathione. This complex was refined at a resolution of 1.45 A. It contains the added ligand in one molecule of the asymmetric unit and glutathione in the other. CONCLUSIONS: The arrangement of ligands around the zinc ions includes a water molecule, presumably in the form of a hydroxide ion, coordinated to both metal ions. This hydroxide ion is situated 2.9 A from the carbonyl carbon of the substrate in such a position that it could act as the nucleophile during catalysis. The reaction mechanism may also have implications for the action of metallo-beta-lactamases.
DiseaseDisease
Known diseases associated with this structure: Glyoxalase II deficiency OMIM:[138760]
About this StructureAbout this Structure
1QH5 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Hydroxyacylglutathione hydrolase, with EC number 3.1.2.6 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue., Cameron AD, Ridderstrom M, Olin B, Mannervik B, Structure. 1999 Sep 15;7(9):1067-78. PMID:10508780
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