Molecular Mechanism of Acetate Transport through the Acetate Channel SatP

doi:10.1021/acs.jcim.8b00975

	Molecular Mechanism of Acetate Transport through the Acetate Channel SatP
	Wu, Meng1,2,3 ; Sun, Liping1 ; Zhou, Qingtong1 ; Peng, Yao1 ; Liu, Zhijie1,2 ; Zhao, Suwen1,2
	2019-05
发表期刊	JOURNAL OF CHEMICAL INFORMATION AND MODELING (IF:5.6[JCR-2023],5.9[5-Year])
ISSN	1549-9596
卷号	59 期号:5 页码:2374-2382
发表状态	已发表
DOI	10.1021/acs.jcim.8b00975
摘要	Acetate is a central metabolite that plays a key role in almost all organisms, and acetate channels are often essential for their survival. Recently solved structures of the acetate channel Succinate-Acetate Permease (SatP) provide an atomic view of its closed state. However, the open state of the channel, the key residue conformational changes that trigger the channel to open, and the free energy barrier of acetate transportation remain elusive. To address these questions, we performed microsecond time scale molecular dynamics (MD) simulations and umbrella sampling. Several acetate passing events were observed in the MD trajectories with the application of an external electric field. Further analyses reveal the molecular mechanism of the channel opening, which results from the repacking of key residues, such as Gln50 and Phe17, as well as the subsequent outward movement of all transmembrane helices. Our simulations show that acetate is always surrounded by several water molecules when passing through the channel. Furthermore, a high energy barrier of 15 kcal/mol was observed from the free energy profile generated by umbrella sampling on the closed state of the channel. Our study deepens the understanding of the molecular mechanism of acetate transport through the channel SatP and is expected to facilitate the drug discovery on this target.
收录类别	SCI ; SCIE
语种	英语
资助项目	NSFC[31800633]
WOS研究方向	Pharmacology & Pharmacy ; Chemistry ; Computer Science
WOS类目	Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Computer Science, Information Systems ; Computer Science, Interdisciplinary Applications
WOS记录号	WOS:000469884900063
出版者	AMER CHEMICAL SOC
WOS关键词	DYNAMICS SIMULATIONS ; AMBER ; PERMEATION ; PROTEIN ; SELECTIVITY ; ACCURACY ; SOFTWARE ; SYSTEM ; FAMILY ; FOCA
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/49015
专题	生命科学与技术学院_博士生 iHuman研究所_特聘教授组_Andrej Sali组 iHuman研究所_特聘教授组_Raymond Stevens组 iHuman研究所_PI研究组_刘志杰组 iHuman研究所_PI研究组_赵素文组
通讯作者	Zhao, Suwen
作者单位	1.ShanghaiTech Univ, iHuman Inst, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
第一作者单位	iHuman研究所; 生命科学与技术学院
通讯作者单位	iHuman研究所; 生命科学与技术学院
第一作者的第一单位	iHuman研究所
推荐引用方式 GB/T 7714	Wu, Meng,Sun, Liping,Zhou, Qingtong,et al. Molecular Mechanism of Acetate Transport through the Acetate Channel SatP[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING,2019,59(5):2374-2382.
APA	Wu, Meng,Sun, Liping,Zhou, Qingtong,Peng, Yao,Liu, Zhijie,&Zhao, Suwen.(2019).Molecular Mechanism of Acetate Transport through the Acetate Channel SatP.JOURNAL OF CHEMICAL INFORMATION AND MODELING,59(5),2374-2382.
MLA	Wu, Meng,et al."Molecular Mechanism of Acetate Transport through the Acetate Channel SatP".JOURNAL OF CHEMICAL INFORMATION AND MODELING 59.5(2019):2374-2382.