3PE6

Crystal Structure of a soluble form of human MGLL in complex with an inhibitor

3PE6 の概要

• エントリーDOI: 10.2210/pdb3pe6/pdb
• 関連するPDBエントリー: 3HJU 3JW8 3JWE
• 分子名称: Monoglyceride lipase, (2-cyclohexyl-1,3-benzoxazol-6-yl){3-[4-(pyrimidin-2-yl)piperazin-1-yl]azetidin-1-yl}methanone (3 entities in total)
• 機能のキーワード: alpha-beta hydrolase fold, lipase, 2-arachidonyl-glycerol, membrane associated, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 33637.67

構造登録者

Schubert, C.,Schalk-Hih, C. (登録日: 2010-10-25, 公開日: 2011-03-02, 最終更新日: 2023-09-06)

主引用文献

Schalk-Hihi, C.,Schubert, C.,Alexander, R.,Bayoumy, S.,Clemente, J.C.,Deckman, I.,DesJarlais, R.L.,Dzordzorme, K.C.,Flores, C.M.,Grasberger, B.,Kranz, J.K.,Lewandowski, F.,Liu, L.,Ma, H.,Maguire, D.,Macielag, M.J.,McDonnell, M.E.,Mezzasalma Haarlander, T.,Miller, R.,Milligan, C.,Reynolds, C.,Kuo, L.C.
Crystal structure of a soluble form of human monoglyceride lipase in complex with an inhibitor at 1.35 A resolution.
Protein Sci., 20:670-683, 2011

PubMed Abstract: A high-resolution structure of a ligand-bound, soluble form of human monoglyceride lipase (MGL) is presented. The structure highlights a novel conformation of the regulatory lid-domain present in the lipase family as well as the binding mode of a pharmaceutically relevant reversible inhibitor. Analysis of the structure lacking the inhibitor indicates that the closed conformation can accommodate the native substrate 2-arachidonoyl glycerol. A model is proposed in which MGL undergoes conformational and electrostatic changes during the catalytic cycle ultimately resulting in its dissociation from the membrane upon completion of the cycle. In addition, the study outlines a successful approach to transform membrane associated proteins, which tend to aggregate upon purification, into a monomeric and soluble form.

PubMed: 21308848
DOI: 10.1002/pro.596

実験手法

X-RAY DIFFRACTION (1.35 Å)