6SSS

Crystal structure of Human Microsomal Glutathione S-Transferase 2

6SSS の概要

• エントリーDOI: 10.2210/pdb6sss/pdb
• 分子名称: Microsomal glutathione S-transferase 2, SULFATE ION, SODIUM ION, ... (8 entities in total)
• 機能のキーワード: er membrane protein, glutathione transferase, mapeg, mgst2, integral membrane enzyme, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 107407.59

構造登録者

Thulasingam, M.,Nji, E.,Haeggstrom, J.Z. (登録日: 2019-09-09, 公開日: 2021-02-03, 最終更新日: 2024-01-24)

主引用文献

Thulasingam, M.,Orellana, L.,Nji, E.,Ahmad, S.,Rinaldo-Matthis, A.,Haeggstrom, J.Z.
Crystal structures of human MGST2 reveal synchronized conformational changes regulating catalysis.
Nat Commun, 12:1728-1728, 2021

PubMed Abstract: Microsomal glutathione S-transferase 2 (MGST2) produces leukotriene C, key for intracrine signaling of endoplasmic reticulum (ER) stress, oxidative DNA damage and cell death. MGST2 trimer restricts catalysis to only one out of three active sites at a time, but the molecular basis is unknown. Here, we present crystal structures of human MGST2 combined with biochemical and computational evidence for a concerted mechanism, involving local unfolding coupled to global conformational changes that regulate catalysis. Furthermore, synchronized changes in the biconical central pore modulate the hydrophobicity and control solvent influx to optimize reaction conditions at the active site. These unique mechanistic insights pertain to other, structurally related, drug targets.

PubMed: 33741927
DOI: 10.1038/s41467-021-21924-8

実験手法

X-RAY DIFFRACTION (2.498 Å)