scholarly journals Structural basis of cyclic 1,3‐diene forming acyl‐coenzyme A dehydrogenases

ChemBioChem ◽  
2021 ◽  
Author(s):  
Johannes Kung ◽  
Anne-Katrin Meier ◽  
Max Willistein ◽  
Sina Weidenweber ◽  
Ulrike Demmer ◽  
...  
Author(s):  
Hongwu Qian ◽  
Xin Zhao ◽  
Renhong Yan ◽  
Shuai Gao ◽  
Xue Sun ◽  
...  

SummaryAcyl-coenzyme A: cholesterol acyltransferases (ACATs) catalyze acyl transfer from acyl-coenzyme A (CoA) to cholesterol to generate cholesteryl ester, which is the primary form for cellular storage and plasma transport of cholesterol. Because of their close relationship with cholesterol metabolism, ACATs represent potential drug target for the treatment of atherosclerosis and other cholesterol-related disorders. Here we present the cryo-EM structure of human ACAT1 at 3.3 Å resolution for dimer of dimers and 3.0 Å for a dimer. Each protomer consists of nine transmembrane segments that enclose a cytosolic (C) and a transmembrane (T) tunnel. The tunnels, each accommodating an elongated density, converge at the predicted catalytic site. Structure-guided mutational analyses suggest the cytosolic and lateral entry for acyl-CoA and cholesterol, respectively. Our structural, biochemical, and mass spectrometric characterizations reveal the catalytic mechanism and substrate preference for unsaturated acyl chain by ACAT1.


1967 ◽  
Vol 242 (9) ◽  
pp. 2111-2115 ◽  
Author(s):  
Lauro Galzigna ◽  
Carlo R. Rossi ◽  
Lodovico Sartorelli ◽  
David M. Gibson

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