000060708 001__ 60708
000060708 005__ 20200221144154.0
000060708 0247_ $$2doi$$a10.1038/nchembio.2019
000060708 0248_ $$2sideral$$a94764
000060708 037__ $$aART-2016-94764
000060708 041__ $$aeng
000060708 100__ $$0(orcid)0000-0002-4680-937X$$aValero-González, J.
000060708 245__ $$aA proactive role of water molecules in acceptor recognition by protein O-fucosyltransferase 2
000060708 260__ $$c2016
000060708 5060_ $$aAccess copy available to the general public$$fUnrestricted
000060708 5203_ $$aProtein O-fucosyltransferase 2 (POFUT2) is an essential enzyme that fucosylates serine and threonine residues of folded thrombospondin type 1 repeats (TSRs). To date, the mechanism by which this enzyme recognizes very dissimilar TSRs has been unclear. By engineering a fusion protein, we report the crystal structure of Caenorhabditis elegans POFUT2 (CePOFUT2) in complex with GDP and human TSR1 that suggests an inverting mechanism for fucose transfer assisted by a catalytic base and shows that nearly half of the TSR1 is embraced by CePOFUT2. A small number of direct interactions and a large network of water molecules maintain the complex. Site-directed mutagenesis demonstrates that POFUT2 fucosylates threonine preferentially over serine and relies on folded TSRs containing the minimal consensus sequence C-X-X-S/T-C. Crystallographic and mutagenesis data, together with atomic-level simulations, uncover a binding mechanism by which POFUT2 promiscuously recognizes the structural fingerprint of poorly homologous TSRs through a dynamic network of water-mediated interactions.
000060708 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/CTQ2012-36365$$9info:eu-repo/grantAgreement/ES/MICINN/CTQ2013-44367-C2-2-P$$9info:eu-repo/grantAgreement/ES/MICINN/BFU2010-19504$$9info:eu-repo/grantAgreement/EC/FP7/283570/EU/Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities/BIOSTRUCT-X$$9info:eu-repo/grantAgreement/ES/DGA/B89
000060708 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000060708 590__ $$a15.066$$b2016
000060708 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b5 / 287 = 0.017$$c2016$$dQ1$$eT1
000060708 592__ $$a8.945$$b2016
000060708 593__ $$aMolecular Biology$$c2016$$dQ1
000060708 593__ $$aCell Biology$$c2016$$dQ1
000060708 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000060708 700__ $$aLeonhard-Melief, C.
000060708 700__ $$aLira-Navarrete, E.
000060708 700__ $$0(orcid)0000-0003-0105-4337$$aJiménez-Osés, G.
000060708 700__ $$aHernández-Ruiz, C.
000060708 700__ $$aPallarés, M.C.
000060708 700__ $$0(orcid)0000-0003-3608-4720$$aYruela, I.$$uUniversidad de Zaragoza
000060708 700__ $$aVasudevan, D.
000060708 700__ $$0(orcid)0000-0001-7460-5916$$aLostao, A.$$uUniversidad de Zaragoza
000060708 700__ $$aCorzana, F.
000060708 700__ $$aTakeuchi, H.
000060708 700__ $$aHaltiwanger, R.S.
000060708 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, R.$$uUniversidad de Zaragoza
000060708 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000060708 773__ $$g12, 4 (2016), 240-246$$pNat. Chem. Biol.$$tNature Chemical Biology$$x1552-4450
000060708 8564_ $$s2096935$$uhttps://zaguan.unizar.es/record/60708/files/texto_completo.pdf$$yPostprint
000060708 8564_ $$s48494$$uhttps://zaguan.unizar.es/record/60708/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000060708 909CO $$ooai:zaguan.unizar.es:60708$$particulos$$pdriver
000060708 951__ $$a2020-02-21-13:08:36
000060708 980__ $$aARTICLE