K. Moreland - Structural insights into the stereochemistry of the cyclooxygenase reaction

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      Publication Details (including relevant citation   information):

      Nature

      Vol. 405, No. 6782, pg. 97-101 (2000)

      ISSN: 0028-0836 (Print)

      DOI: 10.1038/35011103

      Abstract:

      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.

      Address (URL): http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citati on&list_uids=10811226