Comparative analyses of the β-tubulin gene and molecular modeling reveal molecular insight into the colchicine resistance in kinetoplastids organisms.

ABSTRACT: Differential susceptibility to microtubule agents has been demonstrated between mammalian cells and kinetoplastid organisms such as Leishmania spp. and Trypanosoma spp. The aims of this study were to identify and characterize the architecture of the putative colchicine binding site of Leishmania spp. and investigate the molecular basis of colchicine resistance. We cloned and sequenced the β-tubulin gene of Leishmania (Viannia) guyanensis and established the theoretical 3D model of the protein, using the crystallographic structure of the bovine protein as template. We identified mutations on the Leishmania β-tubulin gene sequences on regions related to the putative colchicine-binding pocket, which generate amino acid substitutions and changes in the topology of this region, blocking the acc

SUBMITTER: Luis L 

PROVIDER: S-EPMC3780476 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature