{"doi":"10.1101/2024.02.26.582189","title":"Oxygen affinities of DosT and DosS sensor kinases with implications for hypoxia adaptation in <i>Mycobacterium tuberculosis</i>","abstract":"Abstract DosT and DosS are heme-based kinases involved in sensing and signaling O 2 tension in the microenvironment of Mycobacterium tuberculosis ( Mtb ). Under conditions of low O 2 , they activate &gt;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 2 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 -1 s -1 and 2.8 s -1 , respectively for DosT, and 7.2 μM -1 s -1 and 3.3 s -1 , respectively for DosS. Remarkably, these tighter O 2 binding constants correlate with distinct stages of hypoxia-induced non-replicating persistence in the Wayne model of Mtb . This knowledge opens doors to deconvoluting the intricate interplay between hypoxia adaptation stages and the signal transduction capabilities of these important heme-based O 2 sensors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490133,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9602,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1076708,"name":"Eaindra Yee","orcid":"0000-0002-1726-9271","position":1,"is_corresponding":false},{"id":1076709,"name":"Anoop R. Damodaran","orcid":"0000-0002-2094-9956","position":2,"is_corresponding":false},{"id":1076710,"name":"Ambika Bhagi‐Damodaran","orcid":"0000-0002-4901-074X","position":3,"is_corresponding":false},{"id":1077231,"name":"Elizabeth A. Apiche","orcid":null,"position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":null,"created_at":"2026-07-19T02:08:32.775003Z","pmid":"38464195","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}