4AL1

Crystal structure of Human PS-1 GSH-analog complex

4AL1 の概要

• エントリーDOI: 10.2210/pdb4al1/pdb
• 関連するPDBエントリー: 4AL0
• 分子名称: PROSTAGLANDIN E SYNTHASE, octyl beta-D-glucopyranoside, PALMITIC ACID, ... (6 entities in total)
• 機能のキーワード: isomerase, membrane protein, lipid biosynthesis
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18526.15

構造登録者

Sjogren, T.,Nord, J.,Ek, M.,Johansson, P.,Liu, G.,Geschwindner, S. (登録日: 2012-02-29, 公開日: 2013-02-06, 最終更新日: 2023-12-20)

主引用文献

Sjogren, T.,Nord, J.,Ek, M.,Johansson, P.,Liu, G.,Geschwindner, S.
Crystal Structure of Microsomal Prostaglandin E2 Synthase Provides Insight Into Diversity in the Mapeg Superfamily.
Proc.Natl.Acad.Sci.USA, 110:3806-, 2013

PubMed Abstract: Prostaglandin E2 (PGE2) is a key mediator in inflammatory response. The main source of inducible PGE2, microsomal PGE2 synthase-1 (mPGES-1), has emerged as an interesting drug target for treatment of pain. To support inhibitor design, we have determined the crystal structure of human mPGES-1 to 1.2 Å resolution. The structure reveals three well-defined active site cavities within the membrane-spanning region in each monomer interface of the trimeric structure. An important determinant of the active site cavity is a small cytosolic domain inserted between transmembrane helices I and II. This extra domain is not observed in other structures of proteins within the MAPEG (Membrane-Associated Proteins involved in Eicosanoid and Glutathione metabolism) superfamily but is likely to be present also in microsomal GST-1 based on sequence similarity. An unexpected feature of the structure is a 16-Å-deep cone-shaped cavity extending from the cytosolic side into the membrane-spanning region. We suggest a potential role for this cavity in substrate access. Based on the structure of the active site, we propose a catalytic mechanism in which serine 127 plays a key role. We have also determined the structure of mPGES-1 in complex with a glutathione-based analog, providing insight into mPGES-1 flexibility and potential for structure-based drug design.

PubMed: 23431194
DOI: 10.1073/PNAS.1218504110

実験手法

X-RAY DIFFRACTION (1.95 Å)