Multiple pathways promote dynamical coupling between catalytic domains in Escherichia coli prolyl-tRNA synthetase.
Multiple pathways promote dynamical coupling between catalytic domains in Escherichia coli prolyl-tRNA synthetase.
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DOI：
10.1021/bi400079h
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发表时间：
2013-06-25
期刊：
影响因子：
2.9
通讯作者：
Hati, Sanchita
中科院分区：
文献类型：
--
作者：
Johnson, James M.;Sanford, Brianne L.;Strom, Alexander M.;Tadayon, Stephanie N.;Lehman, Brent P.;Zirbes, Arrianna M.;Bhattacharyya, Sudeep;Musier-Forsyth, Karin;Hati, Sanchita
氨酰-tRNA合成酶是催化氨基酸与其同源tRNA共价连接的多结构域酶。功能域之间的串扰是这一过程的先决条件。本论文研究了大肠杆菌脯氨酰-tRNA合成酶（Ec ProRS）中位点间通讯的分子机制。早期的研究表明，参与相关运动的进化保守/共进化残基对于模块蛋白中功能构象变化从一个位点传播到另一个位点至关重要。在这里，进行分子模拟和基于生物信息学的分析，以确定动态耦合和进化上受约束的残基，这些残基形成Ec ProRS的氨酰化和编辑结构域之间的残基-残基相互作用的连续途径。这项研究的结果表明，这两个结构域之间存在着多种途径，以保持酶功能所必需的动态耦合。此外，这些相互作用网络中的残基通常是高度保守的。途径上残基的定点变化对酶功能和动力学具有显著影响，这表明沿着这些途径的任何扰动沿着破坏两个功能结构域之间有效通信所需的天然残基-残基相互作用。自由能分析表明，一个通路内的残基之间的通信，以及通路之间的串扰是重要的协调功能的不同结构域的Ec ProRS的有效催化。
Aminoacyl-tRNA synthetases are multi-domain enzymes that catalyze covalent attachment of amino acids to their cognate tRNA. Cross-talk between functional domains is a prerequisite for this process. In the present study, we investigate the molecular mechanism of site-to-site communication in Escherichia coli prolyl-tRNA synthetase (Ec ProRS). Earlier studies have demonstrated that evolutionarily conserved/co-evolved residues that are engaged in correlated motion are critical for the propagation of functional conformational changes from one site to another in modular proteins. Here, molecular simulation and bioinformatics-based analysis was performed to identify dynamically coupled and evolutionarily constrained residues that form contiguous pathways of residue-residue interactions between the aminoacylation and editing domains of Ec ProRS. The results of this study suggest that multiple pathways exist between these two domains to maintain the dynamic coupling essential for enzyme function. Moreover, residues in these interaction networks are generally highly conserved. Site-directed changes of on-pathway residues have a significant impact on enzyme function and dynamics suggesting that any perturbation along these pathways disrupts the native residue-residue interactions that are required for effective communication between the two functional domains. Free energy analysis revealed that communication between residues within a pathway, as well as cross-talk between pathways are important to coordinate functions of different domains of Ec ProRS for efficient catalysis.
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DOI：
10.1016/j.str.2009.06.008
发表时间：
2009-08-12
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
del Sol A;Tsai CJ;Ma B;Nussinov R
通讯作者：
Nussinov R
影响因子：
2.9
作者：
Bhattacharyya, Moitrayee;Vishyeshwara, Saraswathi
通讯作者：
Vishyeshwara, Saraswathi
DOI：
10.1073/pnas.0503388102
发表时间：
2005-12-06
影响因子：
11.1
作者：
Bu, ZM;Biehl, R;Callaway, DJE
通讯作者：
Callaway, DJE
影响因子：
4.8
作者：
Hati, Sanchita;Ziervogel, Brigitte;Musier-Forsyth, Karin
通讯作者：
Musier-Forsyth, Karin
DOI：
10.1007/s00249-011-0754-8
发表时间：
2011-12
影响因子：
2
作者：
Bryn Fenwick, R.;Esteban-Martin, Santi;Salvatella, Xavier
通讯作者：
Salvatella, Xavier