{"doi":"10.3390/molecules25102384","title":"Discovery of a Natural Product That Binds to the Mycobacterium tuberculosis Protein Rv1466 Using Native Mass Spectrometry","abstract":"Elucidation of the mechanism of action of compounds with cellular bioactivity is important for progressing compounds into future drug development. In recent years, phenotype-based drug discovery has become the dominant approach to drug discovery over target-based drug discovery, which relies on the knowledge of a specific drug target of a disease. Still, when targeting an infectious disease via a high throughput phenotypic assay it is highly advantageous to identifying the compound’s cellular activity. A fraction derived from the plant Polyalthia sp. showed activity against Mycobacterium tuberculosis at 62.5 μge/μL. A known compound, altholactone, was identified from this fraction that showed activity towards M. tuberculosis at an minimum inhibitory concentration (MIC) of 64 μM. Retrospective analysis of a target-based screen against a TB proteome panel using native mass spectrometry established that the active fraction was bound to the mycobacterial protein Rv1466 with an estimated pseudo-Kd of 42.0 ± 6.1 µM. Our findings established Rv1466 as the potential molecular target of altholactone, which is responsible for the observed in vivo toxicity towards M. tuberculosis.","journal":"Molecules","year":2020,"id":102305,"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":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":499599,"name":"I. Darren Grice","orcid":"0000-0001-9218-457X","position":1,"is_corresponding":false},{"id":499600,"name":"Jianying Han","orcid":"0000-0003-4402-6598","position":2,"is_corresponding":false},{"id":411890,"name":"Yunjiang Feng","orcid":"0000-0003-2412-1213","position":3,"is_corresponding":false},{"id":411891,"name":"Angela Di Capua","orcid":"0000-0001-6960-0715","position":4,"is_corresponding":false},{"id":412854,"name":"Tin Mak","orcid":null,"position":5,"is_corresponding":false},{"id":500304,"name":"Joseph A. Laureanti","orcid":null,"position":6,"is_corresponding":false},{"id":411892,"name":"Garry W. Buchko","orcid":"0000-0002-3639-1061","position":7,"is_corresponding":false},{"id":411893,"name":"Peter J. Myler","orcid":"0000-0002-0056-0513","position":8,"is_corresponding":false},{"id":283182,"name":"Gregory M. Cook","orcid":"0000-0001-8349-1500","position":9,"is_corresponding":false},{"id":411895,"name":"Ronald J. Quinn","orcid":"0000-0002-4022-2623","position":10,"is_corresponding":false},{"id":411894,"name":"Miaomiao Liu","orcid":"0000-0003-0930-3617","position":11,"is_corresponding":false},{"id":500303,"name":"Ali R. Elnaas","orcid":null,"position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T22:40:51.552773Z","pmid":"32455540","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":[]}