Molecular Dynamics Study of Substrate Specificity in Group Ⅰ Nucleoside Hydrolases
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- 英文论文题名：Molecular Dynamics Study of Substrate Specificity in Group Ⅰ Nucleoside Hydrolases
- 论文作者：Fangfang Fan ; Nanhao Chen ; Zexing Cao ; Ruibo Wu
- 英文论文作者：Fangfang Fan ; Nanhao Chen ; Zexing Cao ; Ruibo Wu ; State Key Laboratory of Physical Chemistry of Solid Surfaces and Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry ; College of Chemistry and Chemical Engineering ; Xiamen University ; School of Pharmaceutical Sciences ; East Campus ; Sun Yat-sen University
- 年：2016
- 作者机构：State Key Laboratory of Physical Chemistry of Solid Surfaces and Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry, College of Chemistry and Chemical Engineering, Xiamen University;School of Pharmaceutical Sciences, East Campus, Sun Yat-sen University;
- 英文论文关键词：Nucleoside hydrolases ; MD simulations ; QM/MM
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第十九分会：化学中的量子与经典动力学
- 语种：英文
- 分类号：O629.8
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第十九分会 ; 化学中的量子与经典动力学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：79k
- 原文格式：D
- 会议级别：全国
摘要
Nucleoside hydrolases(NHs) are a class of enzymes that hydrolyze the N-glycosidic bond between the base and sugar groups of selected nucleosides. The homology group Ⅰconsists of both nonspecific and pyrimidine-specific NHs, which share a high degree(30–70%) of sequence identity but have distinct substrate specificities. It is still unknown whether that IU-NHs are acquired-function mutants of CU-NHs or CU-NH enzymes could be endowed with specific active-site features to selectively discriminate the leaving group of pyrimidine nucleosides. Herein molecular dynamics(MD) simulations in combination with state-of-the-art quantum mechanics and molecular mechanics(QM/MM) MD simulations have been used to explore the regulation mechanism of the enzymatic hydrolysis. The present results indicate that there are different working strategies resposible for nonspecific and pyrimidine-specific NHs. Moreover, different key residues around the active pocket of these distinct NHs and two flexible loops 1 and 2 have been found to play an important role in manipulating their hydrolytic decompositions.
Nucleoside hydrolases(NHs) are a class of enzymes that hydrolyze the N-glycosidic bond between the base and sugar groups of selected nucleosides. The homology group Ⅰconsists of both nonspecific and pyrimidine-specific NHs, which share a high degree(30–70%) of sequence identity but have distinct substrate specificities. It is still unknown whether that IU-NHs are acquired-function mutants of CU-NHs or CU-NH enzymes could be endowed with specific active-site features to selectively discriminate the leaving group of pyrimidine nucleosides. Herein molecular dynamics(MD) simulations in combination with state-of-the-art quantum mechanics and molecular mechanics(QM/MM) MD simulations have been used to explore the regulation mechanism of the enzymatic hydrolysis. The present results indicate that there are different working strategies resposible for nonspecific and pyrimidine-specific NHs. Moreover, different key residues around the active pocket of these distinct NHs and two flexible loops 1 and 2 have been found to play an important role in manipulating their hydrolytic decompositions.
Nucleoside hydrolases(NHs) are a class of enzymes that hydrolyze the N-glycosidic bond between the base and sugar groups of selected nucleosides. The homology group Ⅰconsists of both nonspecific and pyrimidine-specific NHs, which share a high degree(30–70%) of sequence identity but have distinct substrate specificities. It is still unknown whether that IU-NHs are acquired-function mutants of CU-NHs or CU-NH enzymes could be endowed with specific active-site features to selectively discriminate the leaving group of pyrimidine nucleosides. Herein molecular dynamics(MD) simulations in combination with state-of-the-art quantum mechanics and molecular mechanics(QM/MM) MD simulations have been used to explore the regulation mechanism of the enzymatic hydrolysis. The present results indicate that there are different working strategies resposible for nonspecific and pyrimidine-specific NHs. Moreover, different key residues around the active pocket of these distinct NHs and two flexible loops 1 and 2 have been found to play an important role in manipulating their hydrolytic decompositions.
引文
[1]Versées,W.;Steyaert,J.Curr.Opin.Struct.Biol.2003,13:731.
[2]Arivett,B.;Farone,M.;Masiragani,R.;Burden,A.;Judge,B.;Osinloye,A.;Minici,C.;Degano,M.;Robinson,M.;Kline,P.Biochim.Biophys.Acta.2014,1844:656.
[3]Chen,N.;Zhao,Y.;Lu,J.;Wu,R.;Cao,Z.J.Chem.Theory Comput.2015,11:3180.
[2]Arivett,B.;Farone,M.;Masiragani,R.;Burden,A.;Judge,B.;Osinloye,A.;Minici,C.;Degano,M.;Robinson,M.;Kline,P.Biochim.Biophys.Acta.2014,1844:656.
[3]Chen,N.;Zhao,Y.;Lu,J.;Wu,R.;Cao,Z.J.Chem.Theory Comput.2015,11:3180.