6L48

Structure of the human sterol O-acyltransferase 1 in resting state

6L48 の概要

• エントリーDOI: 10.2210/pdb6l48/pdb
• EMDBエントリー: 0832
• 分子名称: Sterol O-acyltransferase 1, CHOLESTEROL (2 entities in total)
• 機能のキーワード: soat, acat, mboat, membrane protein, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 115362.86

構造登録者

Chen, L.,Guan, C.,Niu, Y. (登録日: 2019-10-16, 公開日: 2020-04-29, 最終更新日: 2024-03-27)

主引用文献

Guan, C.,Niu, Y.,Chen, S.C.,Kang, Y.,Wu, J.X.,Nishi, K.,Chang, C.C.Y.,Chang, T.Y.,Luo, T.,Chen, L.
Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor.
Nat Commun, 11:2478-2478, 2020

PubMed Abstract: Sterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family. It catalyzes the esterification of cholesterol to generate cholesteryl esters for cholesterol storage. SOAT1 is a target to treat several human diseases. However, its structure and mechanism remain elusive since its discovery. Here, we report the structure of human SOAT1 (hSOAT1) determined by cryo-EM. hSOAT1 is a tetramer consisted of a dimer of dimer. The structure of hSOAT1 dimer at 3.5 Å resolution reveals that a small molecule inhibitor CI-976 binds inside the catalytic chamber and blocks the accessibility of the active site residues H460, N421 and W420. Our results pave the way for future mechanistic study and rational drug design targeting hSOAT1 and other mammalian MBOAT family members.

PubMed: 32424158
DOI: 10.1038/s41467-020-16288-4

実験手法

ELECTRON MICROSCOPY (3.5 Å)