Molecular modeling and dynamics studies of cytidylate kinase from Mycobacterium tuberculosis H37Rv

被引：12

作者：

Caceres, Rafael Andrade ^{[1
,2
]}

Saraiva Macedo Timmers, Luis Fernando ^{[1
]}

Vivan, Ana Luiza ^{[1
]}

Schneider, Cristopher Zandon ^{[3
]}

Basso, Luiz Augusto ^{[3
]}

De Azevedo, Walter Filgueira, Jr. ^{[1
]}

Santos, Diogenes Santiago ^{[3
]}

机构：

[1] Pontificia Univ Catolica Rio Grande do Sul, Lab Bioquim Estrut, Fac Biiociencias, Porto Alegre, RS, Brazil

[2] Pontificia Univ Catolica Rio Grande do Sul, Program Pos Grad Biol Celular & Mol, Porto Alegre, RS, Brazil

[3] Pontificia Univ Catolica Rio Grande do Janeiro, Inst Pesquisas Biomed, Ctr Pesquisas Biol Mol & Func, Porto Alegre, RS, Brazil

来源：

JOURNAL OF MOLECULAR MODELING | 2008年 / 14卷 / 05期

关键词：

cytidine 5 '-monophosphate; enzyme substrate specificity; molecular dynamics; molecular modeling; Mycobacterium tuberculosis;

D O I：

10.1007/s00894-008-0291-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Bacterial cytidylate kinase or cytidine monophosphate kinase (CMP kinase) catalyses the phosphoryl transfer from ATP to CMP and dCMP, resulting in the formation nucleoside diphosphates. In eukaryotes, CMP/UMP kinase catalyses the conversion of UMP and CMP to, respectively, UDP and CDP with high efficiency. This work describes for the first time a model of bacterial cytidylate kinase or cytidine monophosphate kinase (CMP kinase) from mycobacterium tuberculosis (MtCMPK). We modeled MtPCMPK in apo form and in complex with cytidine 5'-monophosphate (CMP) to try to determine the structural basis for specificity. Comparative analysis of the model of MtCMPK allowed identification of structural features responsible for ligand affinities. Analysis of the molecular dynamics simulations of these two systems indicates the structural features responsible for the stability of the structure, and may help in the identification of new inhibitors for this enzyme.

引用

页码：427 / 434

页数：8

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