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    Annu Rev Biophys Biomol Struct. 2003;32:183-206. Epub 2003 Feb 5.

    The structure of mammalian cyclooxygenases.

    Source

    Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824-1319, USA. garavito@msu.edu

    Abstract

    Cyclooxygenases-1 and -2 (COX-1 and COX-2, also known as prostaglandin H2 synthases-1 and -2) catalyze the committed step in prostaglandin synthesis. COX-1 and -2 are of particular interest because they are the major targets of nonsteroidal antiinflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2-selective inhibitors. Inhibition of the COXs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces the incidence of fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of COXs relate mechanistically to cyclooxygenase and peroxidase catalysis and how alternative fatty acid substrates bind within the COX active site. We further examine how NSAIDs interact with COXs and how differences in the structure of COX-2 result in enhanced selectivity toward COX-2 inhibitors.

    PMID:
    12574066
    [PubMed - indexed for MEDLINE]

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