6WF2

Crystal structure of mouse SCD1 with a diiron center

6WF2 の概要

• エントリーDOI: 10.2210/pdb6wf2/pdb
• 分子名称: Acyl-CoA desaturase 1, FE (III) ION, S-{(3R,5R,9R)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9-trihydroxy-8,8-dimethyl-3,5-dioxido-10,14-dioxo-2,4,6-trioxa-11,15-diaza-3lambda~5~,5lambda~5~-diphosphaheptadecan-17-yl} (9Z)-octadec-9-enethioate (non-preferred name) (3 entities in total)
• 機能のキーワード: scd1, membrane enzyme, diiron center, electron transfer, double bond formation, membrane protein, oxidoreductase
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81428.60

構造登録者

Shen, J.,Zhou, M. (登録日: 2020-04-03, 公開日: 2020-06-17, 最終更新日: 2023-10-18)

主引用文献

Shen, J.,Wu, G.,Tsai, A.L.,Zhou, M.
Structure and Mechanism of a Unique Diiron Center in Mammalian Stearoyl-CoA Desaturase.
J.Mol.Biol., 432:5152-5161, 2020

PubMed Abstract: Stearoyl-CoA desaturase 1 (SCD1) is a membrane-embedded metalloenzyme that catalyzes the formation of a double bond on a saturated acyl-CoA. SCD1 has a diiron center and its proper function requires an electron transport chain composed of NADH (or NADPH), cytochrome b reductase (bR), and cytochrome b (cyt b). Since SCD1 is a key regulator in fat metabolism and is required for survival of cancer cells, there is intense interest in targeting SCD1 for various metabolic diseases and cancers. Crystal structures of human and mouse SCD1 were reported recently; however, both proteins have two zinc ions instead of two iron ions in the catalytic center, and as a result, the enzymes are inactive. Here we report a general approach for incorporating iron into heterologously expressed proteins in HEK293 cells. We produced mouse SCD1 that contains a diiron center and visualized its diiron center by solving its crystal structure to 3.5 Å. We assembled the entire electron transport chain using the purified soluble domains of cyt b and bR, and the purified mouse SCD1, and we showed that three proteins coordinate to produce proper products. These results established an in vitro system that allows precise perturbations of the electron transport chain for the understanding of the catalytic mechanism in SCD1.

PubMed: 32470559
DOI: 10.1016/j.jmb.2020.05.017

実験手法

X-RAY DIFFRACTION (3.51 Å)