The productive conformation of arachidonic acid bound to prostaglandin synthase.
Malkowski, M.G., Ginell, S.L., Smith, W.L., Garavito, R.M.(2000) Science 289: 1933-1937
- PubMed: 10988074
- DOI: https://doi.org/10.1126/science.289.5486.1933
- Primary Citation of Related Structures:
1DIY - PubMed Abstract:
Prostaglandin H synthase-1 and -2 (PGHS-1 and -2) catalyze the committed step in prostaglandin synthesis and are targets for nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin. We have determined the structure of PGHS-1 at 3 angstrom resolution with arachidonic acid (AA) bound in a chemically productive conformation. The fatty acid adopts an extended L-shaped conformation that positions the 13proS hydrogen of AA for abstraction by tyrosine-385, the likely radical donor. A space also exists for oxygen addition on the antarafacial surface of the carbon in the 11-position (C-11). While this conformation allows endoperoxide formation between C-11 and C-9, it also implies that a subsequent conformational rearrangement must occur to allow formation of the C-8/C-12 bond and to position C-15 for attack by a second molecule of oxygen.
Organizational Affiliation:
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824-1319, USA.