{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Apiche EA"],"funding":["NIGMS NIH HHS"],"pubmed_abstract":["DosT and DosS are heme-based kinases involved in sensing and signaling O<sub>2</sub> tension in the microenvironment of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>). Under conditions of low O<sub>2</sub>, 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 O<sub>2</sub> binding affinities of DosT and DosS to show that their equilibrium dissociation constants are 3.3±1 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<sup>-1</sup>s<sup>-1</sup> and 2.8 s<sup>-1</sup>, respectively for DosT, and 7.2 μM<sup>-1</sup>s<sup>-1</sup> and 3.3 s<sup>-1</sup>, respectively for DosS. Remarkably, these tighter O<sub>2</sub> binding constants correlate with distinct stages of hypoxia-induced non-replicating persistence in the Wayne model of <i>Mtb</i>. This knowledge opens doors to deconvoluting the intricate interplay between hypoxia adaptation stages and the signal transduction capabilities of these important heme-based O<sub>2</sub> sensors."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2024.02.26.582189"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10925234"],"repository":["biostudies-literature"],"pubmed_title":["Oxygen affinities of DosT and DosS sensor kinases with implications for hypoxia adaptation in <i>Mycobacterium tuberculosis</i>."],"pmcid":["PMC10925234"],"funding_grant_id":["R35 GM138277"],"pubmed_authors":["Damodaran AR","Bhagi-Damodaran A","Yee E","Apiche EA"],"additional_accession":[]},"is_claimable":false,"name":"Oxygen affinities of DosT and DosS sensor kinases with implications for hypoxia adaptation in <i>Mycobacterium tuberculosis</i>.","description":"DosT and DosS are heme-based kinases involved in sensing and signaling O<sub>2</sub> tension in the microenvironment of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>). Under conditions of low O<sub>2</sub>, 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 O<sub>2</sub> binding affinities of DosT and DosS to show that their equilibrium dissociation constants are 3.3±1 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<sup>-1</sup>s<sup>-1</sup> and 2.8 s<sup>-1</sup>, respectively for DosT, and 7.2 μM<sup>-1</sup>s<sup>-1</sup> and 3.3 s<sup>-1</sup>, respectively for DosS. Remarkably, these tighter O<sub>2</sub> binding constants correlate with distinct stages of hypoxia-induced non-replicating persistence in the Wayne model of <i>Mtb</i>. This knowledge opens doors to deconvoluting the intricate interplay between hypoxia adaptation stages and the signal transduction capabilities of these important heme-based O<sub>2</sub> sensors.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-05-29T03:18:00.356Z","creation":"2025-04-07T07:07:39.928Z"},"accession":"S-EPMC10925234","cross_references":{"pubmed":["38464195"],"doi":["10.1101/2024.02.26.582189"]}}