| Structural insights into the stereochemistry of the cyclooxygenase reaction. | |
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MedLine Citation:
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PMID: 10811226 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cyclooxygenases are bifunctional enzymes that catalyse the first committed step in the synthesis of prostaglandins, thromboxanes and other eicosanoids. The two known cyclooxygenases isoforms share a high degree of amino-acid sequence similarity, structural topology and an identical catalytic mechanism. Cyclooxygenase enzymes catalyse two sequential reactions in spatially distinct, but mechanistically coupled active sites. The initial cyclooxygenase reaction converts arachidonic acid (which is achiral) to prostaglandin G2 (which has five chiral centres). The subsequent peroxidase reaction reduces prostaglandin G2 to prostaglandin H2. Here we report the co-crystal structures of murine apo-cyclooxygenase-2 in complex with arachidonic acid and prostaglandin. These structures suggest the molecular basis for the stereospecificity of prostaglandin G2 synthesis. |
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Authors:
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J R Kiefer; J L Pawlitz; K T Moreland; R A Stegeman; W F Hood; J K Gierse; A M Stevens; D C Goodwin; S W Rowlinson; L J Marnett; W C Stallings; R G Kurumbail |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Nature Volume: 405 ISSN: 0028-0836 ISO Abbreviation: Nature Publication Date: 2000 May |
Date Detail:
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Created Date: 2000-05-23 Completed Date: 2000-05-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 97-101 Citation Subset: IM |
Affiliation:
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Searle Discovery Research, Monsanto Company, St Louis, Missouri 63198, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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PDB/1CVU; 1DCX; 1DD0; 1DDX |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoenzymes / chemistry, metabolism Arachidonic Acid / chemistry*, metabolism Binding Sites Crystallography, X-Ray Cyclooxygenase 2 Isoenzymes / chemistry*, metabolism Mice Models, Molecular Prostaglandin H2 Prostaglandin-Endoperoxide Synthases / chemistry*, metabolism Prostaglandins H / chemistry*, metabolism Protein Conformation Recombinant Proteins / chemistry, metabolism Stereoisomerism |
| Chemical | |
Reg. No./Substance:
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0/Apoenzymes; 0/Isoenzymes; 0/Prostaglandins H; 0/Recombinant Proteins; 42935-17-1/Prostaglandin H2; 506-32-1/Arachidonic Acid; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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