Molecular Dynamics Simulations on the Mechanism of Transporting Methylamine and Ammonia by Ammonium Transporter AmtB
文献类型：期刊论文
| 作者 | Wang, Jinan2; Yang, Huaiyu2; Zuo, Zhili1; Yan, Xiuhua2; Wang, Yong2; Luo, Xiaomin2 ; Jiang, Hualiang2; Chen, Kaixian2; Zhu, Weiliang2,3
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| 刊名 | JOURNAL OF PHYSICAL CHEMISTRY B
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| 出版日期 | 2010-11-25 |
| 卷号 | 114期号:46页码:15172-15179 |
| ISSN号 | 1520-6106 |
| DOI | 10.1021/jp104508k |
| 文献子类 | Article |
| 英文摘要 | AmtB is one of the ammonium transporter proteins facilitating the ammonium transport across the cellular membranes. Experimentally, the substrate used in in vitro studies is the radio labeled [C-14]methylammonium, rather than ammonium itself. To explore the similarity and difference of the conduction mechanism of methylamine and ammonia molecules through AmtB, molecular dynamics simulations on 22 carefully designed systems were performed, which demonstrated that methylamine could be automatically transported in a very similar way to ammonia. The driving force for the conduction is mainly the hydrogen bond network comprising His168, His318, and Tyr32, working in coordination with NH-pi interaction with residue Trp212. Then, Ser263 translocated the substrates from the exit gate into the cytoplasm by hydrogen bond interaction. The aromatic ring of Trp212 acted like a springboard to facilitate the translocation of the substrates from site Am2 to Am4 via NH-pi interaction. Without the mediation of Trp212, further movement of substrate in the channel would be hampered by the strong hydrogen bonding from His168. In agreement with experimental results, the substrates could be transported by W212F mutant but not by W212A within the simulation time as long as 20 ns. In addition, we predicted that the mutants S263D and S263C remain the function of the transporter but S263A does not. The difference of transporting the two substrates is that methylamine involves more hydrophobic interactions than ammonia. In conclusion, methylamine molecule is a good mimic for investigating the translocation mechanism of ammonium transporter AmtB. |
| WOS关键词 | CHANNEL PROTEIN AMTB ; ESCHERICHIA-COLI ; CRYSTAL-STRUCTURE ; SACCHAROMYCES-CEREVISIAE ; DEPROTONATION MECHANISM ; COMPLEX-FORMATION ; HYDROPHOBIC PORE ; PI-INTERACTION ; GLNK ; FAMILY |
| 资助项目 | National Natural Science Foundation[20721003] ; CAS foundation[KSCX2-YW-R-208] ; CAS Foundation[KSCX2-YW-R-168] ; Shanghai ST Foundation[09540703900] ; National Science & Technology Major Project[2009ZX09301-001] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000284287700046 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278715]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Zhu, Weiliang |
| 作者单位 | 1.Curtin Univ Technol, Sch Biomed Sci, Perth, WA 6485, Australia; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 3.E China Univ Sci & Technol, Sch Sci, Shanghai 200237, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Jinan,Yang, Huaiyu,Zuo, Zhili,et al. Molecular Dynamics Simulations on the Mechanism of Transporting Methylamine and Ammonia by Ammonium Transporter AmtB[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2010,114(46):15172-15179. |
| APA | Wang, Jinan.,Yang, Huaiyu.,Zuo, Zhili.,Yan, Xiuhua.,Wang, Yong.,...&Zhu, Weiliang.(2010).Molecular Dynamics Simulations on the Mechanism of Transporting Methylamine and Ammonia by Ammonium Transporter AmtB.JOURNAL OF PHYSICAL CHEMISTRY B,114(46),15172-15179. |
| MLA | Wang, Jinan,et al."Molecular Dynamics Simulations on the Mechanism of Transporting Methylamine and Ammonia by Ammonium Transporter AmtB".JOURNAL OF PHYSICAL CHEMISTRY B 114.46(2010):15172-15179. |
入库方式： OAI收割
来源：上海药物研究所
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