000150787 001__ 150787
000150787 005__ 20251017144651.0
000150787 0247_ $$2doi$$a10.1038/s41598-025-87535-1
000150787 0248_ $$2sideral$$a142858
000150787 037__ $$aART-2025-142858
000150787 041__ $$aeng
000150787 100__ $$aWeinhäupl, Katharina
000150787 245__ $$aIdentification of new ClpC1-NTD binders for Mycobacterium tuberculosis drug development
000150787 260__ $$c2025
000150787 5060_ $$aAccess copy available to the general public$$fUnrestricted
000150787 5203_ $$aMtbClpC1 is a promising drug target against tuberculosis. Recent studies have shown that several natural product antibiotics targeting the unfoldase N-terminal domain can impair MtbClpC1 function resulting in cell death. While the pharmacological properties of these natural product antibiotics prevent their use in the clinic, similar molecules binding to the same binding pockets can result in new drugs against Mtb. Here we demonstrate that we successfully used in silico screening to identify new ClpC1 N-terminal domain binders with micromolar affinity from a small compound library. In addition, we experimentally demonstrate that the new compounds bind to the same pockets used by the natural product antibiotics and inhibit ClpC1 function.
000150787 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/PI21-00394$$9info:eu-repo/grantAgreement/ES/MICINN/AEI/PID2021-127296OB-I00
000150787 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000150787 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000150787 700__ $$aMeuret, Louis
000150787 700__ $$aDesrat, Sandy
000150787 700__ $$aRoussy, Fanny
000150787 700__ $$aMorellet, Nelly
000150787 700__ $$aBeaupierre, Sandra
000150787 700__ $$aGuillou, Catherine
000150787 700__ $$avan Heijenoort, Carine
000150787 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, Olga$$uUniversidad de Zaragoza
000150787 700__ $$0(orcid)0000-0002-1232-6310$$aVega, Sonia
000150787 700__ $$aWolf, Ian
000150787 700__ $$aAkopian, Tatos
000150787 700__ $$aKrandor, Olga
000150787 700__ $$aRubin, Eric
000150787 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, Adrian$$uUniversidad de Zaragoza
000150787 700__ $$aGauto, Diego
000150787 700__ $$aFraga, Hugo
000150787 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000150787 773__ $$g15, 1 (2025), 4146 [14 pp.]$$pSci. rep. (Nat. Publ. Group)$$tScientific reports (Nature Publishing Group)$$x2045-2322
000150787 8564_ $$s5779353$$uhttps://zaguan.unizar.es/record/150787/files/texto_completo.pdf$$yVersión publicada
000150787 8564_ $$s2657076$$uhttps://zaguan.unizar.es/record/150787/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000150787 909CO $$ooai:zaguan.unizar.es:150787$$particulos$$pdriver
000150787 951__ $$a2025-10-17-14:36:35
000150787 980__ $$aARTICLE