000168249 001__ 168249
000168249 005__ 20260130124311.0
000168249 0247_ $$2doi$$a10.1016/j.ijbiomac.2025.149851
000168249 0248_ $$2sideral$$a147764
000168249 037__ $$aART-2026-147764
000168249 041__ $$aeng
000168249 100__ $$aGarcia-Franco, Paula M.
000168249 245__ $$aZinc cofactor in human histone deacetylase 8: Requirement for function and opportunity for drug discovery
000168249 260__ $$c2026
000168249 5060_ $$aAccess copy available to the general public$$fUnrestricted
000168249 5203_ $$aHDAC8 (histone deacetylase 8), a class I HDAC, is a promising target for different disorders: X-linked intellectual disability, fibrotic disease, cancer, and several neuropathological diseases. The structural and functional similarity between HDACs hinders the development of selective HDAC8 inhibitors. To date, no drugs based on competitive inhibition have been approved. In order to identify weaknesses in HDAC8 amenable to drug discovery, we report here a comprehensive thermodynamic characterization of the structural stability and its modulation by the interaction with its zinc (Zn2+) cofactor using a combination of experimental and computational techniques. HDAC8 represents an interesting example of an allosteric protein in the broad sense, in which its cofactor, the zinc ion, modulates its conformational equilibrium. The native, inactive, zinc-free state is physiologically relevant considering that the intracellular concentration of zinc is very low and may constitute a
valid target for drug discovery.
000168249 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B08-24R$$9info:eu-repo/grantAgreement/ES/DGA/B25-23R$$9info:eu-repo/grantAgreement/ES/DGA/E45-23R$$9info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI21-00394$$9info:eu-repo/grantAgreement/ES/ISCIII/i-PFIS-IFI23-00020$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BES-2017-080739$$9info:eu-repo/grantAgreement/ES/MCIU/PID2024-160408OB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/AEI/PID2021-127296OB-I00$$9info:eu-repo/grantAgreement/ES/MICINN-AEI/PRTR-C17.I1$$9info:eu-repo/grantAgreement/ES/MICIU/JDC2023-052992-I
000168249 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000168249 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000168249 700__ $$aFalcó-Martí, F. Javier$$uUniversidad de Zaragoza
000168249 700__ $$aJeblaoui, Hajar
000168249 700__ $$aAsencio del Rio, Marta
000168249 700__ $$0(orcid)0000-0003-1885-4365$$aOrtega-Alarcon, David
000168249 700__ $$0(orcid)0000-0002-1232-6310$$aVega, Sonia
000168249 700__ $$0(orcid)0000-0002-1896-7805$$aGalano-Frutos, Juan J.
000168249 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, Olga$$uUniversidad de Zaragoza
000168249 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, Adrian$$uUniversidad de Zaragoza
000168249 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000168249 773__ $$g339, 26 (2026), 149851 [16 pp.]$$pInt. j. biol. macromol.$$tInternational journal of biological macromolecules$$x0141-8130
000168249 8564_ $$s3009551$$uhttps://zaguan.unizar.es/record/168249/files/texto_completo.pdf$$yVersión publicada
000168249 8564_ $$s2596892$$uhttps://zaguan.unizar.es/record/168249/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000168249 909CO $$ooai:zaguan.unizar.es:168249$$particulos$$pdriver
000168249 951__ $$a2026-01-30-12:20:44
000168249 980__ $$aARTICLE