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Dynamic Interactions Between Brilliant Green and MscL Investigated by Solid-State NMR Spectroscopy and Molecular Dynamics Simulations

文献类型：期刊论文

作者Ma, Shaojie1,2,3,4; Zhang, Yan1,6; Zhang, Xuning1,3,4; Xie, Huayong1; Tong, Qiong1; Yu, Kunqian2; Yang, Jun1,3,4,5,6
刊名CHEMISTRY-A EUROPEAN JOURNAL
出版日期2022-11-21
页码12
关键词Antibiotic Brilliant Green mechanosensitive channel of large conductance (MscL) molecule dynamics simulations solid-state NMR
ISSN号0947-6539
DOI10.1002/chem.202202106
通讯作者Tong, Qiong(tongqiong@wipm.ac.cn) ; Yu, Kunqian(yukunqian@simm.ac.cn) ; Yang, Jun(yangjun@wipm.ac.cn)
英文摘要The mechanosensitive ion channel of large conductance (MscL) is a promising template for the development of new antibiotics due to its high conservation and uniqueness to microbes. Brilliant green (BG), a triarylmethane dye, has been identified as a new antibiotic targeted MscL. However, the detailed binding sites to MscL and the dynamic pathway of BG through the MscL channel remain unknown. Here, the dynamic interactions between BG and MscL were investigated using solid-state NMR spectroscopy and molecule dynamics (MD) simulations. Residue site-specific binding sites of BG to the MscL channel were identified by solid-state NMR. In addition, MD simulations revealed that BG conducts through the MscL channel via residues along the inner surface of the pore sequentially, in which the strong hydrophobic interactions between BG and hydrophobic residues F23 and I27 in the hydrophobic gate region of the MscL channel are major restrictions. Particularly, it was demonstrated that BG activates the MscL channel by reducing the hydrophobicity of the F23 in the gate region by water molecules that are bound to BG. Taken together, these simulations and experimental data provide novel insights into the dynamic interactions between BG and MscL, based on which new hydrophobic antibiotics and adjuvants targeting MscL can be developed.
WOS关键词MECHANOSENSITIVE CHANNEL ; LARGE-CONDUCTANCE ; ION-CHANNEL ; BINDING ; ACTIVATION ; MECHANISM ; TARGETS ; POCKETS ; PROTON ; GATE
资助项目National Key R&D Program of China ; National Natural Science Foundation of China ; Chinese Academy of Sciences ; China Postdoctoral Science Foundation ; [2017YFA0505400] ; [21927801] ; [21904136] ; [21921004] ; [YJKYYQ20190032] ; [2020M672455]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000888306500001
出版者WILEY-V C H VERLAG GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/304560]  
专题新药研究国家重点实验室
通讯作者Tong, Qiong; Yu, Kunqian; Yang, Jun
作者单位1.Chinese Acad Sci, Wuhan Inst Phys & Math, Innovat Acad Precis Measurement Sci & Technol, Natl Ctr Magnet Resonance Wuhan,State Key Lab Magn, Wuhan 430071, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Key Lab Mol Biophys, Minist Educ, Wuhan 430074, Peoples R China
4.Huazhong Univ Sci & Technol, Collaborat Innovat Ctr Brain Sci, Wuhan Natl Lab Optoelect, Wuhan 430074, Peoples R China
5.Huazhong Univ Sci & Technol, Wuhan Natl Lab Optoelect, Wuhan 430074, Peoples R China
6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式
GB/T 7714		 Ma, Shaojie,Zhang, Yan,Zhang, Xuning,et al. Dynamic Interactions Between Brilliant Green and MscL Investigated by Solid-State NMR Spectroscopy and Molecular Dynamics Simulations[J]. CHEMISTRY-A EUROPEAN JOURNAL,2022:12.
APA Ma, Shaojie.,Zhang, Yan.,Zhang, Xuning.,Xie, Huayong.,Tong, Qiong.,...&Yang, Jun.(2022).Dynamic Interactions Between Brilliant Green and MscL Investigated by Solid-State NMR Spectroscopy and Molecular Dynamics Simulations.CHEMISTRY-A EUROPEAN JOURNAL,12.
MLA Ma, Shaojie,et al."Dynamic Interactions Between Brilliant Green and MscL Investigated by Solid-State NMR Spectroscopy and Molecular Dynamics Simulations".CHEMISTRY-A EUROPEAN JOURNAL (2022):12.

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来源：上海药物研究所

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