Nat Struct Biol. 1995 Aug;2(8):637-43.

The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase.

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Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637, USA.

Abstract

Aspirin exerts its anti-inflammatory effects through selective acetylation of serine 530 on prostaglandin H2 synthase (PGHS). Here we present the 3.4 A resolution X-ray crystal structure of PGHS isoform-1 inactivated by the potent aspirin analogue 2-bromoacetoxy-benzoic acid. Acetylation by this analogue abolishes cyclooxygenase activity by steric blockage of the active-site channel and not through a large conformational change. We observe two rotameric states of the acetyl-serine side chain which block the channel to different extents, a result which may explain the dissimilar effects of aspirin on the two PGHS isoforms. We also observe the product salicylic acid binding at a site consistent with its antagonistic effect on aspirin activity.

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Nat Struct Biol. 1995 Aug;2(8):605-6.

PMID:: 7552725; [PubMed - indexed for MEDLINE]

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Structures reported by this article

The Structural Basis Of Aspirin Activity Inferred From The Crystal Structure Of Inactivated Prostaglandin H2 Synthase

PDB: 1PTH

Source: Ovis aries

Method: X-Ray Diffraction

Resolution: 3.4 Å

See all 2 structures...

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