Comparative molecular dynamics simulations identify a salt-sensitive loop responsible for the halotolerant activity of GH5 cellulases
Comparative molecular dynamics simulations identify a salt-sensitive loop responsible for the halotolerant activity of GH5 cellulases
复制标题
比较分子动力学模拟确定了负责 GH5 纤维素酶耐盐活性的盐敏感环
DOI：
10.1080/07391102.2021.1930167
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发表时间：
2021-05
影响因子：
4.4
通讯作者：
Wang Lushan
中科院分区：
文献类型：
--
作者：
Song Yuxuan;Wu Xiuyun;Zhao Yue;Jiang Xukai;Wang Lushan
摘要 耐盐糖苷水解酶（GH）在生物炼制工业中具有广泛的应用潜力。阐明耐盐催化的构效关系对于设计优质生物催化剂至关重要。在这里，我们进行了分子动力学模拟来研究两种 GH5 纤维素酶（即耐盐 Cel5R 和非耐盐 TfCel5A）的结构动力学。通过表征不同盐浓度下的物理性质，结果表明，Cel5R 和 TfCel5A 的整体结构受盐浓度增加的影响很小。然而，基于其在高盐浓度下显着增加的灵活性，从 Cel5R 和 TfCel5A 中鉴定出了盐敏感环。重要的是，与 TfCel5A 相比，Cel5R 的盐敏感环在酶的活性位点周围结合了更多的钠离子和水分子。此外，Cel5R中盐敏感环的独特残基基序形成了更多的分子内氢键，从而稳定了Cel5R在高盐浓度下的活性结构。总的来说，结构和动力学差异可能导致 Cel5R 和 TfCel5A 的不同催化耐卤性。这些发现为耐盐催化提供了机理见解，并将指导具有改进催化性能的 GH5 纤维素酶的配量设计。由Ramaswamy H. Samy 传达图形摘要
Abstract Halotolerant glycoside hydrolases (GH) have broad application potentials in biorefinery industries. Elucidating the structure-activity relationship underlying the halotolerant catalysis is essential to design superior biocatalysts. Here, we performed molecular dynamics simulations to investigate the structural dynamics of two GH5 cellulases, namely the halotolerant Cel5R and non-halotolerant TfCel5A. Through characterizing the physical properties at different salt concentrations, the results revealed that the overall structures of Cel5R and TfCel5A were marginally affected by the increase in salt concentrations. However, a salt-sensitive loop was identified from both Cel5R and TfCel5A based on its significantly increased flexibility at high salt concentrations. Importantly, compared to TfCel5A the salt-sensitive loop of Cel5R engaged more sodium ions and water molecules around the active site of the enzyme. Besides, the unique residue motif of the salt-sensitive loop in Cel5R formed more intramolecular hydrogen bonds, stabilizing the active architecture of Cel5R at high salt concentrations. Collectively, the structural and dynamic differences may contribute to the various catalytic halotolerance of Cel5R and TfCel5A. These findings provide mechanistic insight into the halotolerant catalysis and will guide the ration design of GH5 cellulases with improved catalytic properties. Communicated by Ramaswamy H. Samy Graphical Abstract
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影响因子：
--
作者：
Siglioccolo A;Paiardini A;Piscitelli M;Pascarella S
通讯作者：
Pascarella S
DOI：
10.1016/j.ijbiomac.2019.11.015
发表时间：
2020-07-01
影响因子：
8.2
作者：
Chen Q;Xiao Y;Shakhnovich EI;Zhang W;Mu W
通讯作者：
Mu W
高盐适应的分子特征：基因组的见解和卤素原核生物的蛋白质组组成。
影响因子：
12.3
作者：
Paul S;Bag SK;Das S;Harvill ET;Dutta C
通讯作者：
Dutta C
分子动力学模拟
DOI：
10.1002/9783527651276.ch8
发表时间：
2012
期刊：
The Journal of chemical physics
影响因子：
--
作者：
J. Kärger;D. Ruthven;D. Theodorou
通讯作者：
D. Theodorou
影响因子：
4.4
作者：
D. Benrezkallah;M. Dauchez;A. Krallafa
通讯作者：
D. Benrezkallah;M. Dauchez;A. Krallafa