Insight into the thermostability of thermophilic L-asparaginase and non-thermophilic L-asparaginase II through bioinformatics and structural analysis
Insight into the thermostability of thermophilic L-asparaginase and non-thermophilic L-asparaginase II through bioinformatics and structural analysis
复制标题
通过生物信息学和结构分析深入了解嗜热L-天冬酰胺酶和非嗜热L-天冬酰胺酶II的热稳定性
DOI：
10.1007/s00253-019-09967-w
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发表时间：
2019-09-01
影响因子：
5
通讯作者：
Rao, Zhiming
中科院分区：
文献类型：
--
作者：
Li, Xu;Zhang, Xian;Rao, Zhiming
热稳定性是影响L-天冬酰胺酶在医药和食品工业中应用的重要因素。了解影响L-天冬酰胺酶热稳定性的关键残基和结构对于获得合适的L-天冬酰胺酶候选物是必要的。在这项研究中，特殊的残基和结构，改变了嗜热L-天冬酰胺酶和非嗜热L-天冬酰胺酶II的热稳定性进行了鉴定。将来自四种菌株（即Pyrococcus yayanosiiCH 1（PYA）、耐热热球菌（TGA）、枯草杆菌（BSA II）和大肠杆菌（ECA II））的L-天冬酰胺酶的这些特殊残基和结构互换，揭示了PYA的第51位和第298位残基（对应第57位，ECA II的第305位残基）作为负责嗜热L-天冬酰胺酶和非嗜热L-天冬酰胺酶II的热稳定性的关键残基。此外，C末端的紧密性、环的刚性以及活性位点周围的低表面电荷对L-天冬酰胺酶的热稳定性具有重要意义。本研究揭示了导致L-天冬酰胺酶II热稳定性差异的关键氨基酸残基和结构，为L-天冬酰胺酶II的热稳定性工程化提供了参考。
Thermostability plays an important role in the application of L-asparaginase in the pharmaceutical and food industries. Understanding the key residues and structures that influence thermostability in L-asparaginase is necessary to obtain suitable L-asparaginase candidates. In this study, special residues and structures that altered thermostability in thermophilic L-asparaginase and non-thermophilic L-asparaginase II were identified. Interchanging these special residues and structures of L-asparaginases from the four strains, that is,Pyrococcus yayanosiiCH1 (PYA),Thermococcus gammatolerans(TGA),Bacillus subtilis(BSA II), andEscherichia coli(ECA II), revealed the 51st and 298th residues of PYA (corresponding to 57th, 305th residues of ECA II) as the key residues responsible for thermal stability of thermophilic L-asparaginase and non-thermophilic L-asparaginase II. Moreover, the C terminal tightness, loop rigidity, and low surface charge around activity sites were of great significance to the thermostability of L-asparaginase. This study therefore revealed the crucial amino acid residues and structures responsible for the difference in thermostability of the thermophilic and non-thermophilic L-asparaginase and provides a reference for engineering thermostability in L-asparaginase II.