Show simple item record

dc.contributor.authorElnaas, Ali R
dc.contributor.authorGrice, Darren
dc.contributor.authorHan, Jianying
dc.contributor.authorFeng, Yunjiang
dc.contributor.authorCapua, Angela Di
dc.contributor.authorMak, Tin
dc.contributor.authorLaureanti, Joseph A
dc.contributor.authorBuchko, Garry W
dc.contributor.authorMyler, Peter J
dc.contributor.authorCook, Gregory
dc.contributor.authorQuinn, Ronald J
dc.contributor.authorLiu, Miaomiao
dc.date.accessioned2020-09-21T01:02:20Z
dc.date.available2020-09-21T01:02:20Z
dc.date.issued2020
dc.identifier.issn1420-3049
dc.identifier.doi10.3390/molecules25102384
dc.identifier.urihttp://hdl.handle.net/10072/397692
dc.description.abstractElucidation 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherMDPI
dc.relation.ispartofpagefrom2384
dc.relation.ispartofissue10
dc.relation.ispartofjournalMolecules
dc.relation.ispartofvolume25
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchOrganic Chemistry
dc.subject.fieldofresearchTheoretical and Computational Chemistry
dc.subject.fieldofresearchcode0304
dc.subject.fieldofresearchcode0305
dc.subject.fieldofresearchcode0307
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsPhysical Sciences
dc.subject.keywordsBiochemistry & Molecular Biology
dc.subject.keywordsChemistry, Multidisciplinary
dc.titleDiscovery of a Natural Product That Binds to the Mycobacterium tuberculosis Protein Rv1466 Using Native Mass Spectrometry
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationElnaas, AR; Grice, D; Han, J; Feng, Y; Capua, AD; Mak, T; Laureanti, JA; Buchko, GW; Myler, PJ; Cook, G; Quinn, RJ; Liu, M, Discovery of a Natural Product That Binds to the Mycobacterium tuberculosis Protein Rv1466 Using Native Mass Spectrometry, Molecules, 2020, 25 (10), pp. 2384
dcterms.dateAccepted2020-05-18
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-09-21T00:59:12Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorGrice, Darren D.
gro.griffith.authorLiu, Miaomiao
gro.griffith.authorElnaas, Ali
gro.griffith.authorHan, Jianying
gro.griffith.authorQuinn, Ronald J.
gro.griffith.authorFeng, Yun J.
gro.griffith.authorDi Capua, Angela
gro.griffith.authorMak, Tin


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record