Molecular modeling and dynamics studies of cytidylate kinase from Mycobacterium tuberculosis H37Rv.
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.
Caceres
Rafael Andrade
RA
Programa de Pós Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Macedo Timmers
Luís Fernando Saraiva
LF
Vivan
Ana Luiza
AL
Schneider
Cristopher Zandoná
CZ
Basso
Luiz Augusto
LA
De Azevedo
Walter Filgueira
WF
Santos
Diogenes Santiago
DS
D000595:Amino Acid Sequence; D003198:Computer Simulation; D003568:Cytidine Monophosphate / Q000737:chemistry; D004926:Escherichia coli / Q000201:enzymology; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009703:Nucleoside-Phosphate Kinase / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D008024:Ligands; C019979:cytidylate kinase; D009703:Nucleoside-Phosphate Kinase; D003568:Cytidine Monophosphate