1PTH

The Structural Basis of Aspirin Activity Inferred from the Crystal Structure of Inactivated Prostaglandin H2 Synthase

1PTH の概要

• エントリーDOI: 10.2210/pdb1pth/pdb
• 分子名称: 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)
• 機能のキーワード: dioxygenase, peroxidase, oxidoreductase
• 由来する生物種: Ovis aries (sheep)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 136399.07

構造登録者

Loll, P.J.,Picot, D.,Garavito, R.M. (登録日: 1995-04-11, 公開日: 1996-04-11, 最終更新日: 2025-03-26)

主引用文献

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

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: 7552725
DOI: 10.1038/nsb0895-637

実験手法

X-RAY DIFFRACTION (3.4 Å)