4ZYO

Crystal Structure of Human Integral Membrane Stearoyl-CoA Desaturase with Substrate

4ZYO の概要

• エントリーDOI: 10.2210/pdb4zyo/pdb
• 分子名称: Acyl-CoA desaturase, ZINC ION, STEAROYL-COENZYME A, ... (5 entities in total)
• 機能のキーワード: membrane protein, desaturase, metal binding protein, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Endoplasmic reticulum membrane ; Multi-pass membrane protein : O00767
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38473.64

構造登録者

Wang, H.,Klein, M.G.,Lane, W.,Snell, G.,Levin, I.,Li, K.,Zou, H.,Sang, B.-C. (登録日: 2015-05-21, 公開日: 2015-06-17, 最終更新日: 2024-03-06)

主引用文献

Wang, H.,Klein, M.G.,Zou, H.,Lane, W.,Snell, G.,Levin, I.,Li, K.,Sang, B.C.
Crystal structure of human stearoyl-coenzyme A desaturase in complex with substrate.
Nat.Struct.Mol.Biol., 22:581-585, 2015

PubMed Abstract: Stearoyl-coenzyme A desaturase-1 (SCD1) has an important role in lipid metabolism, and SCD1 inhibitors are potential therapeutic agents for the treatment of metabolic diseases and cancers. Here we report the 3.25-Å crystal structure of human SCD1 in complex with its substrate, stearoyl-coenzyme A, which defines the new SCD1 dimetal catalytic center and reveals the determinants of substrate binding to provide insights into the catalytic mechanism of desaturation of the stearoyl moiety. The structure also provides a mechanism for localization of SCD1 in the endoplasmic reticulum: human SCD1 folds around a tight hydrophobic core formed from four long α-helices that presumably function as an anchor spanning the endoplasmic reticulum membrane. Furthermore, our results provide a framework for the rational design of pharmacological inhibitors targeting the SCD1 enzyme.

PubMed: 26098317
DOI: 10.1038/nsmb.3049

実験手法

X-RAY DIFFRACTION (3.25 Å)