Oxygen affinities of DosT and DosS sensor kinases with implications for hypoxia adaptation in Mycobacterium tuberculosis.

ABSTRACT: DosT and DosS are heme-based kinases involved in sensing and signaling O₂ tension in the microenvironment of Mycobacterium tuberculosis (Mtb). Under conditions of low O₂, they activate >50 dormancy-related genes and play a pivotal role in the induction of dormancy and associated drug resistance during tuberculosis infection. In this work, we reexamine the O₂ binding affinities of DosT and DosS to show that their equilibrium dissociation constants are 3.3±1.0 μM and 0.46±0.08 μM respectively, which are six to eight-fold stronger than what has been widely referred to in literature. Furthermore, stopped-flow kinetic studies reveal association and dissociation rate constants of 0.84 μM^-1 s^-1 and 2.8 s^-1, respectively for DosT, a

SUBMITTER: Apiche EA 

PROVIDER: S-EPMC11665979 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature