000056262 001__ 56262
000056262 005__ 20210121082905.0
000056262 0247_ $$2doi$$a10.1038/ncomms9923
000056262 0248_ $$2sideral$$a92702
000056262 037__ $$aART-2015-92702
000056262 041__ $$aeng
000056262 100__ $$aBuey, R.M.
000056262 245__ $$aGuanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases
000056262 260__ $$c2015
000056262 5060_ $$aAccess copy available to the general public$$fUnrestricted
000056262 5203_ $$aInosine-5'-monophosphate dehydrogenase (IMPDH) plays key roles in purine nucleotide metabolism and cell proliferation. Although IMPDH is a widely studied therapeutic target, there is limited information about its physiological regulation. Using Ashbya gossypii as a model, we describe the molecular mechanism and the structural basis for the allosteric regulation of IMPDH by guanine nucleotides. We report that GTP and GDP bind to the regulatory Bateman domain, inducing octamers with compromised catalytic activity. Our data suggest that eukaryotic and prokaryotic IMPDHs might have developed different regulatory mechanisms, with GTP/GDP inhibiting only eukaryotic IMPDHs. Interestingly, mutations associated with human retinopathies map into the guanine nucleotide-binding sites including a previously undescribed non-canonical site and disrupt allosteric inhibition. Together, our results shed light on the mechanisms of the allosteric regulation of enzymes mediated by Bateman domains and provide a molecular basis for certain retinopathies, opening the door to new therapeutic approaches.
000056262 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P$$9info:eu-repo/grantAgreement/EC/FP7/293831/EU/Modulating EB protein interactions through small molecules/EB-SxIP
000056262 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000056262 590__ $$a11.329$$b2015
000056262 591__ $$aMULTIDISCIPLINARY SCIENCES$$b3 / 62 = 0.048$$c2015$$dQ1$$eT1
000056262 592__ $$a6.287$$b2015
000056262 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2015$$dQ1
000056262 593__ $$aPhysics and Astronomy (miscellaneous)$$c2015$$dQ1
000056262 593__ $$aChemistry (miscellaneous)$$c2015$$dQ1
000056262 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000056262 700__ $$aLedesma-Amaro, R.
000056262 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza
000056262 700__ $$aBalsera, M.
000056262 700__ $$aChagoyen, M.
000056262 700__ $$aDe Pereda, J.M.
000056262 700__ $$aRevuelta, J.L.
000056262 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000056262 773__ $$g6 (2015), 8923[11 pp]$$pNATURE COMMUNICATIONS$$tNature Communications$$x2041-1723
000056262 8564_ $$s2092434$$uhttps://zaguan.unizar.es/record/56262/files/texto_completo.pdf$$yVersión publicada
000056262 8564_ $$s73676$$uhttps://zaguan.unizar.es/record/56262/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000056262 909CO $$ooai:zaguan.unizar.es:56262$$particulos$$pdriver
000056262 951__ $$a2021-01-21-08:17:45
000056262 980__ $$aARTICLE