Bioinformatic and mutational studies of related toxin-antitoxin pairs in Mycobacterium tuberculosis predict and identify key functional residues.

ABSTRACT: Mycobacterium tuberculosis possesses an unusually large representation of type II toxin-antitoxin (TA) systems, whose functions and targets are mostly unknown. To better understand the basis of their unique expansion and to probe putative functional similarities among these systems, here we computationally and experimentally investigated their sequence relationships. Bioinformatic and phylogenetic investigations revealed that 51 sequences of the VapBC toxin family group into paralogous sub-clusters. On the basis of conserved sequence fingerprints within paralogues, we predicted functional residues and residues at the putative TA interface that are useful to evaluate TA interactions. Substitution of these likely functional residues abolished the toxin's growth-inhibitory activity. Fu

SUBMITTER: Tandon H 

PROVIDER: S-EPMC6556569 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature