1DIY

CRYSTAL STRUCTURE OF ARACHIDONIC ACID BOUND IN THE CYCLOOXYGENASE ACTIVE SITE OF PGHS-1

Summary for 1DIY

• Entry DOI: 10.2210/pdb1diy/pdb
• Related: 1CVU 1DDX 1PGE 1PRH 1PTH
• Descriptor: PROSTAGLANDIN H2 SYNTHASE-1, 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: arachidonic acid, membrane protein, peroxidase, dioxygenase, oxidoreductase
• Biological source: Ovis aries (sheep)
• Total number of polymer chains: 1
• Total formula weight: 67577.28

Authors

Malkowski, M.G.,Ginell, S.L.,Smith, W.L.,Garavito, R.M. (deposition date: 1999-11-30, release date: 2000-09-22, Last modification date: 2024-10-30)

Primary citation

Malkowski, M.G.,Ginell, S.L.,Smith, W.L.,Garavito, R.M.
The productive conformation of arachidonic acid bound to prostaglandin synthase.
Science, 289:1933-1937, 2000

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.

PubMed: 10988074
DOI: 10.1126/science.289.5486.1933

Experimental method

X-RAY DIFFRACTION (3 Å)