1PTH
The Structural Basis of Aspirin Activity Inferred from the Crystal Structure of Inactivated Prostaglandin H2 Synthase
Summary for 1PTH
| Entry DOI | 10.2210/pdb1pth/pdb |
| Descriptor | PROSTAGLANDIN H2 SYNTHASE-1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | dioxygenase, peroxidase, oxidoreductase |
| Biological source | Ovis aries (sheep) |
| Total number of polymer chains | 2 |
| Total formula weight | 136399.07 |
| Authors | Loll, P.J.,Picot, D.,Garavito, R.M. (deposition date: 1995-04-11, release date: 1996-04-11, Last modification date: 2025-03-26) |
| Primary citation | Loll, P.J.,Picot, D.,Garavito, R.M. The structural basis of aspirin activity inferred from the crystal structure of inactivated prostaglandin H2 synthase. Nat.Struct.Biol., 2:637-643, 1995 Cited by PubMed 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. PubMed: 7552725DOI: 10.1038/nsb0895-637 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.4 Å) |
Structure validation
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