000885766 001__ 885766
000885766 005__ 20220930130255.0
000885766 0247_ $$2doi$$a10.3390/ijms21207683
000885766 0247_ $$2ISSN$$a1422-0067
000885766 0247_ $$2ISSN$$a1661-6596
000885766 0247_ $$2Handle$$a2128/26799
000885766 0247_ $$2altmetric$$aaltmetric:92547040
000885766 0247_ $$2pmid$$a33081390
000885766 0247_ $$2WOS$$aWOS:000585770700001
000885766 037__ $$aFZJ-2020-04074
000885766 082__ $$a540
000885766 1001_ $$00000-0002-0157-532X$$aBukhdruker, Sergey$$b0
000885766 245__ $$aHydroxylation of Antitubercular Drug Candidate, SQ109, by Mycobacterial Cytochrome P450
000885766 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2020
000885766 3367_ $$2DRIVER$$aarticle
000885766 3367_ $$2DataCite$$aOutput Types/Journal article
000885766 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1610976911_9652
000885766 3367_ $$2BibTeX$$aARTICLE
000885766 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000885766 3367_ $$00$$2EndNote$$aJournal Article
000885766 520__ $$aSpreading of the multidrug-resistant (MDR) strains of the one of the most harmful pathogen Mycobacterium tuberculosis (Mtb) generates the need for new effective drugs. SQ109 showed activity against resistant Mtb and already advanced to Phase II/III clinical trials. Fast SQ109 degradation is attributed to the human liver Cytochrome P450s (CYPs). However, no information is available about interactions of the drug with Mtb CYPs. Here, we show that Mtb CYP124, previously assigned as a methyl-branched lipid monooxygenase, binds and hydroxylates SQ109 in vitro. A 1.25 Å-resolution crystal structure of the CYP124–SQ109 complex unambiguously shows two conformations of the drug, both positioned for hydroxylation of the ω-methyl group in the trans position. The hydroxylated SQ109 presumably forms stabilizing H-bonds with its target, Mycobacterial membrane protein Large 3 (MmpL3). We anticipate that Mtb CYPs could function as analogs of drug-metabolizing human CYPs affecting pharmacokinetics and pharmacodynamics of antitubercular (anti-TB) drugs.
000885766 536__ $$0G:(DE-HGF)POF3-552$$a552 - Engineering Cell Function (POF3-552)$$cPOF3-552$$fPOF III$$x0
000885766 588__ $$aDataset connected to CrossRef
000885766 7001_ $$0P:(DE-HGF)0$$aVaraksa, Tatsiana$$b1
000885766 7001_ $$0P:(DE-HGF)0$$aGrabovec, Irina$$b2
000885766 7001_ $$00000-0003-2369-1732$$aMarin, Egor$$b3
000885766 7001_ $$0P:(DE-HGF)0$$aShabunya, Polina$$b4
000885766 7001_ $$00000-0003-2514-2606$$aKadukova, Maria$$b5
000885766 7001_ $$0P:(DE-HGF)0$$aGrudinin, Sergei$$b6
000885766 7001_ $$0P:(DE-HGF)0$$aKavaleuski, Anton$$b7
000885766 7001_ $$0P:(DE-HGF)0$$aGusach, Anastasiia$$b8
000885766 7001_ $$0P:(DE-HGF)0$$aGilep, Andrei$$b9
000885766 7001_ $$0P:(DE-Juel1)179072$$aBorshchevskiy, Valentin$$b10$$eCorresponding author
000885766 7001_ $$0P:(DE-HGF)0$$aStrushkevich, Natallia$$b11$$eCorresponding author
000885766 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms21207683$$gVol. 21, no. 20, p. 7683 -$$n20$$p7683 -$$tInternational journal of molecular sciences$$v21$$x1422-0067$$y2020
000885766 8564_ $$uhttps://juser.fz-juelich.de/record/885766/files/Invoice_MDPI_ijms-972270_1853.05EUR.pdf
000885766 8564_ $$uhttps://juser.fz-juelich.de/record/885766/files/Hydroxylation%20of%20Antitubercular%20Drug%20Candidate%2C%20SQ109%2C%20by%20Mycobacterial%20Cytochrome%20P450.pdf$$yOpenAccess
000885766 8564_ $$uhttps://juser.fz-juelich.de/record/885766/files/Invoice_MDPI_ijms-972270_1853.05EUR.pdf?subformat=pdfa$$xpdfa
000885766 8767_ $$8972270$$92020-10-14$$d2020-10-26$$eAPC$$jZahlung erfolgt$$zBelegnr. 1200158314
000885766 909CO $$ooai:juser.fz-juelich.de:885766$$popenCost$$pVDB$$pdriver$$pOpenAPC$$popen_access$$popenaire$$pdnbdelivery
000885766 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)179072$$aForschungszentrum Jülich$$b10$$kFZJ
000885766 9131_ $$0G:(DE-HGF)POF3-552$$1G:(DE-HGF)POF3-550$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lBioSoft – Fundamentals for future Technologies in the fields of Soft Matter and Life Sciences$$vEngineering Cell Function$$x0
000885766 9141_ $$y2020
000885766 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2020-01-02
000885766 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000885766 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bINT J MOL SCI : 2018$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000885766 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$f2020-01-02
000885766 915__ $$0StatID:(DE-HGF)1150$$2StatID$$aDBCoverage$$bCurrent Contents - Physical, Chemical and Earth Sciences$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2020-01-02
000885766 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2020-01-02
000885766 920__ $$lyes
000885766 9201_ $$0I:(DE-Juel1)IBI-7-20200312$$kIBI-7$$lStrukturbiochemie$$x0
000885766 980__ $$ajournal
000885766 980__ $$aVDB
000885766 980__ $$aUNRESTRICTED
000885766 980__ $$aI:(DE-Juel1)IBI-7-20200312
000885766 980__ $$aAPC
000885766 9801_ $$aAPC
000885766 9801_ $$aFullTexts