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Ammonium Transport Proteins with Changes in One of the Conserved Pore Histidines Have Different Performance in Ammonia and Methylamine Conduction

文献类型：期刊论文

作者Wang, Jinan2; Fulford, Tim1; Shao, Qiang2; Javelle, Arnaud1; Yang, Huaiyu2; Zhu, Weiliang2; Merrick, Mike1
刊名PLOS ONE
出版日期2013-05-07
卷号8期号:5
ISSN号1932-6203
DOI10.1371/journal.pone.0062745
文献子类Article
英文摘要Two conserved histidine residues are located near the mid-point of the conduction channel of ammonium transport proteins. The role of these histidines in ammonia and methylamine transport was evaluated by using a combination of in vivo studies, molecular dynamics (MD) simulation, and potential of mean force (PMF) calculations. Our in vivo results showed that a single change of either of the conserved histidines to alanine leads to the failure to transport methylamine but still facilitates good growth on ammonia, whereas double histidine variants completely lose their ability to transport both methylamine and ammonia. Molecular dynamics simulations indicated the molecular basis of the in vivo observations. They clearly showed that a single histidine variant (H168A or H318A) of AmtB confines the rather hydrophobic methylamine more strongly than ammonia around the mutated sites, resulting in dysfunction in conducting the former but not the latter molecule. PMF calculations further revealed that the single histidine variants form a potential energy well of up to 6 kcal/mol for methylamine, impairing conduction of this substrate. Unlike the single histidine variants, the double histidine variant, H168A/H318A, of AmtB was found to lose its unidirectional property of transporting both ammonia and methylamine. This could be attributed to a greatly increased frequency of opening of the entrance gate formed by F215 and F107, in this variant compared to wild-type, with a resultant lowering of the energy barrier for substrate to return to the periplasm.
WOS关键词MOLECULAR-DYNAMICS SIMULATIONS ; AMTB-GLNK COMPLEX ; ESCHERICHIA-COLI ; CHANNEL AMTB ; NITROSOMONAS-EUROPAEA ; FUNCTIONAL-CHARACTERIZATION ; CORYNEBACTERIUM-GLUTAMICUM ; SACCHAROMYCES-CEREVISIAE ; DEPROTONATION MECHANISM ; CRYSTAL-STRUCTURE
资助项目Biotechnology and Biological Sciences Research Council - BBSRC[00000000] ; BBSRC Committee Studentship[00000000] ; Ministry of Science and Technology[2010DFB73280] ; Ministry of Science and Technology[2012AA01A305] ; Ministry of Science and Technology[2012CB910403] ; National Natural Science Foundation[21021063] ; Computer Network Information Center (CNIC)[00000000] ; Chinese Academy of Sciences (CAS)[00000000] ; Shanghai Supercomputing Center (SCC)[00000000]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000319654700061
出版者PUBLIC LIBRARY SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/277620]  
专题药物发现与设计中心
通讯作者Zhu, Weiliang
作者单位1.John Innes Ctr, Dept Mol Microbiol, Norwich, Norfolk, England
2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai 200031, Peoples R China;
推荐引用方式
GB/T 7714		 Wang, Jinan,Fulford, Tim,Shao, Qiang,et al. Ammonium Transport Proteins with Changes in One of the Conserved Pore Histidines Have Different Performance in Ammonia and Methylamine Conduction[J]. PLOS ONE,2013,8(5).
APA Wang, Jinan.,Fulford, Tim.,Shao, Qiang.,Javelle, Arnaud.,Yang, Huaiyu.,...&Merrick, Mike.(2013).Ammonium Transport Proteins with Changes in One of the Conserved Pore Histidines Have Different Performance in Ammonia and Methylamine Conduction.PLOS ONE,8(5).
MLA Wang, Jinan,et al."Ammonium Transport Proteins with Changes in One of the Conserved Pore Histidines Have Different Performance in Ammonia and Methylamine Conduction".PLOS ONE 8.5(2013).

入库方式： OAI收割

来源：上海药物研究所

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