The cyclooxygenase isoforms: structural insights into the conversion of arachidonic acid to prostaglandins.
Despite the marked differences in their physiological roles, the structures and catalytic functions of the cyclooxygenase isozymes COX-1 and -2 are virtually identical. Nevertheless, a handful of amino acid substitutions give rise to subtle differences in ligand binding between the two isoforms. These 'small' alterations of isozyme structure are sufficient to allow the design of new, isoform-selective drugs.
Garavito
R M
RM
Department of Biochemistry, Michigan State University, East Lansing, MI 48824-1319, USA. garavito@pilot.msu.edu
DeWitt
D L
DL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001665:Binding Sites; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019281:Dimerization; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry* / Q000378:metabolism*; D008565:Membrane Proteins; D008958:Models, Molecular; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry* / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005227:Fatty Acids; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases