Homology modeling of wild-type, D516V, and H526L Mycobacterium tuberculosis RNA polymerase and their molecular docking study with inhibitors.
Rifamicyns (Rifs) are antibiotic widely used for the treatment of tuberculosis (TB); nevertheless, their efficacy has been limited by a high percentage of mutations, principally in the rpoB gene. In this work, the first three-dimensional molecular model of the hypothetical structures for the wild-type and D516V and H526L mutants of Mycobacterium tuberculosis (mtRNAP) were elucidated by a homology modeling method. In addition, the orientations and binding affinities of some Rifs with those new structures were investigated. Our findings could be helpful for the design of new more potent rifamycin analogs.
Josa
Daniela
D
Departamento de Química, Universidade Federal de Lavras, Brazil.
da Cunha
Elaine F F
EF
Ramalho
Teodorico C
TC
Souza
Thais C S
TC
Caetano
Melissa S
MS
D019943:Amino Acid Substitution / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D003198:Computer Simulation; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000235:genetics; D030562:Databases, Protein; D004791:Enzyme Inhibitors / Q000737:chemistry*; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D012294:Rifamycins / Q000737:chemistry / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D012294:Rifamycins; D012321:DNA-Directed RNA Polymerases