VadK, a Non-Canonical Kinase that Regulates the Methylcitrate Cycle and is Essential for <i>Mycobacterium tuberculosis</i> Virulence.

ABSTRACT: The evolution of new enzymatic functions is constrained and guided by the architecture of an organism's metabolic and regulatory networks as well as by environmental constraints. Here, we identify a previously uncharacterized kinase that has evolved from pyruvate phosphate dikinase (PPDK). Through biochemical and systems-level analyses, we show that this enzyme, encoded by Rv1127c in Mycobacterium tuberculosis (Mtb), has diverged from its ancestral role in central carbon metabolism to function as a histidine kinase in pathogenic mycobacteria and related species. We designate this enzyme Virulence Associated DiKinase (VadK), reflecting its ability to autophosphorylate and role in coordinating metabolism and virulence. VadK is essential for the utilization of exogenous carbon sources

SUBMITTER: Pascoe J 

PROVIDER: S-EPMC12636432 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature