EMD-0829
Structure of the human sterol O-acyltransferase 1 tetramer in oval shape
EMD-0829
Single-particle8.25 Å
Deposition: 16/10/2019Map released: 29/04/2020
Last modified: 07/10/2020
Sample Organism:
Homo sapiens
Sample: human sterol O-acyltransferase 1 tetramer
Deposition Authors: Chen L, Guan C
Sample: human sterol O-acyltransferase 1 tetramer
Deposition Authors: Chen L, Guan C
Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor.
Guan C,
Niu Y,
Chen SC,
Kang Y 
,
Wu JX,
Nishi K,
Chang CCY ,
Chang TY,
Luo T ,
Chen L
(2020) Nat Commun , 11 , 2478 - 2478
,
Wu JX,
Nishi K,
Chang CCY ,
Chang TY,
Luo T ,
Chen L
(2020) Nat Commun , 11 , 2478 - 2478
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.
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.