1pth
From Proteopedia
The Structural Basis of Aspirin Activity Inferred from the Crystal Structure of Inactivated Prostaglandin H2 Synthase
Structural highlights
FunctionPGH1_SHEEP May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAspirin 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. The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase.,Loll PJ, Picot D, Garavito RM Nat Struct Biol. 1995 Aug;2(8):637-43. PMID:7552725[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found See AlsoReferences
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