title: Molecular modeling and dynamics studies of cytidylate kinase from Mycobacterium tuberculosis H37Rv.
abstract: 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.
authors.affiliation: Programa de Pós Graduação em Biologia Celular e Molecular, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Rafael Andrade
authors.initials: RA
authors.lastname: Caceres
authors.forename: Luís Fernando Saraiva
authors.initials: LF
authors.lastname: Macedo Timmers
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Vivan
authors.forename: Cristopher Zandoná
authors.initials: CZ
authors.lastname: Schneider
authors.forename: Luiz Augusto
authors.initials: LA
authors.lastname: Basso
authors.forename: Walter Filgueira
authors.initials: WF
authors.lastname: De Azevedo
authors.forename: Diogenes Santiago
authors.initials: DS
authors.lastname: Santos
mesh_terms: 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
chemical_list: D008024:Ligands; C019979:cytidylate kinase; D009703:Nucleoside-Phosphate Kinase; D003568:Cytidine Monophosphate