Structural basis for catalysis and substrate specificity of human ACAT1

doi:10.1038/s41586-020-2290-0

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2290-0
	Structural basis for catalysis and substrate specificity of human ACAT1
	Jiao, Huipeng; Wachsmuth, Laurens; Kumari, Snehlata; Schwarzer, Robin; Lin, Juan; Eren, Remzi Onur; Fisher, Amanda; Lane, Rebecca; Young, George R.; Kassiotis, George; Kaiser, William J.; Pasparakis, Manolis
	2020-04-03
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	581 期号:7808 页码:333-+
文章类型	Article
语种	英语
国家	USA; Peoples R China; Australia
英文关键词	The structure of human ACAT1, which catalyses the transfer of an acyl group from acyl-coenzyme A to cholesterol to form cholesteryl ester, is resolved by cryo-electron microscopy. As members of the membrane-bound O-acyltransferase (MBOAT) enzyme family, acyl-coenzyme A:cholesterol acyltransferases (ACATs) catalyse the transfer of an acyl group from acyl-coenzyme A to cholesterol to generate cholesteryl ester, the primary form in which cholesterol is stored in cells and transported in plasma(1). ACATs have gained attention as potential drug targets for the treatment of diseases such as atherosclerosis, Alzheimer' s disease and cancer(2-7). Here we present the cryo-electron microscopy structure of human ACAT1 as a dimer of dimers. Each protomer consists of nine transmembrane segments, which enclose a cytosolic tunnel and a transmembrane tunnel that converge at the predicted catalytic site. Evidence from structure-guided mutational analyses suggests that acyl-coenzyme A enters the active site through the cytosolic tunnel, whereas cholesterol may enter from the side through the transmembrane tunnel. This structural and biochemical characterization helps to rationalize the preference of ACAT1 for unsaturated acyl chains, and provides insight into the catalytic mechanism of enzymes within the MBOAT family(8).
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000532688300004
WOS关键词	COA-CHOLESTEROL ACYLTRANSFERASE ; ACYL-COENZYME ; IDENTIFICATION ; ENZYME ; CELLS ; ATHEROSCLEROSIS ; ESTERIFICATION ; PREGNENOLONE ; PROGRESSION ; INHIBITION
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281428
专题	地球科学资源环境科学气候变化
推荐引用方式 GB/T 7714	Jiao, Huipeng,Wachsmuth, Laurens,Kumari, Snehlata,et al. Structural basis for catalysis and substrate specificity of human ACAT1[J]. NATURE,2020,581(7808):333-+.
APA	Jiao, Huipeng.,Wachsmuth, Laurens.,Kumari, Snehlata.,Schwarzer, Robin.,Lin, Juan.,...&Pasparakis, Manolis.(2020).Structural basis for catalysis and substrate specificity of human ACAT1.NATURE,581(7808),333-+.
MLA	Jiao, Huipeng,et al."Structural basis for catalysis and substrate specificity of human ACAT1".NATURE 581.7808(2020):333-+.