Document Detail

Structural insights into the stereochemistry of the cyclooxygenase reaction.
MedLine Citation:
PMID:  10811226     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  405     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-05-23     Completed Date:  2000-05-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  97-101     Citation Subset:  IM    
Searle Discovery Research, Monsanto Company, St Louis, Missouri 63198, USA.
Data Bank Information
Bank Name/Acc. No.:
PDB/1CVU;  1DCX;  1DD0;  1DDX
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MeSH Terms
Apoenzymes / chemistry,  metabolism
Arachidonic Acid / chemistry*,  metabolism
Binding Sites
Crystallography, X-Ray
Cyclooxygenase 2
Isoenzymes / chemistry*,  metabolism
Models, Molecular
Prostaglandin H2
Prostaglandin-Endoperoxide Synthases / chemistry*,  metabolism
Prostaglandins H / chemistry*,  metabolism
Protein Conformation
Recombinant Proteins / chemistry,  metabolism
Reg. No./Substance:
0/Apoenzymes; 0/Isoenzymes; 0/Prostaglandins H; 0/Recombinant Proteins; 42935-17-1/Prostaglandin H2; 506-32-1/Arachidonic Acid; EC 2; EC Synthases

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