Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/51915
DC FieldValueLanguage
dc.contributor.authorChaikuad, Apirat
dc.contributor.authorKeates, Tracy
dc.contributor.authorVincke, Cécile
dc.contributor.authorKaufholz, Melanie
dc.contributor.authorZenn, Michael
dc.contributor.authorZimmermann, Bastian
dc.contributor.authorGutierrez, Carlos
dc.contributor.authorZhang, Rong Guang
dc.contributor.authorHatzos-Skintges, Catherine
dc.contributor.authorJoachimiak, Andrzej
dc.contributor.authorMuyldermans, Serge
dc.contributor.authorHerberg, Friedrich W.
dc.contributor.authorKnapp, Stefan
dc.contributor.authorMüller, Susanne
dc.contributor.otherMuyldermans, Serge
dc.contributor.otherHerberg, Friedrich
dc.contributor.otherGutierrez, Carlos
dc.contributor.otherMuller-Knapp, Susanne
dc.contributor.otherKnapp, Stefan
dc.date.accessioned2018-11-25T05:22:44Z-
dc.date.available2018-11-25T05:22:44Z-
dc.date.issued2014
dc.identifier.issn0264-6021
dc.identifier.urihttp://hdl.handle.net/10553/51915-
dc.description.abstractGAK (cyclin G-associated kinase) is a key regulator of clathrincoated vesicle trafficking and plays a central role during development. Additionally, due to the unusually high plasticity of its catalytic domain, it is a frequent 'off-target' of clinical kinase inhibitors associated with respiratory side effects of these drugs. In the present paper, we determined the crystal structure of the GAK catalytic domain alone and in complex with specific single-chain antibodies (nanobodies). GAK is constitutively active and weakly associates in solution. The GAK apo structure revealed a dimeric inactive state of the catalytic domain mediated by an unusual activation segment interaction. Co-crystallization with the nanobody NbGAK_4 trapped GAK in a dimeric arrangement similar to the one observed in the apo structure, whereas NbGAK_1 captured the activation segment of monomeric GAK in a well-ordered conformation, representing features of the active kinase. The presented structural and biochemical data provide insight into the domain plasticity of GAK and demonstrate the utility of nanobodies to gain insight into conformational changes of dynamic molecules. In addition, we present structural data on the binding mode of ATP mimetic inhibitors and enzyme kinetic data, which will support rational inhibitor design of inhibitors to reduce the off-target effect on GAK.
dc.publisher0264-6021
dc.relation.ispartofBiochemical Journal
dc.sourceBiochemical Journal[ISSN 0264-6021],v. 459, p. 59-69
dc.subject.otherClathrin
dc.subject.otherReceptor
dc.subject.otherDomain
dc.subject.otherRefinement
dc.subject.otherProteins
dc.subject.otherComplex
dc.subject.otherTools
dc.titleStructure of cyclin G-associated kinase (GAK) trapped in different conformations using nanobodies
dc.typeinfo:eu-repo/semantics/Articlees
dc.typeArticlees
dc.identifier.doi10.1042/BJ20131399
dc.identifier.scopus84896138811
dc.identifier.isi000333718700006
dcterms.isPartOfBiochemical Journal
dcterms.sourceBiochemical Journal[ISSN 0264-6021],v. 459, p. 59-69
dc.contributor.authorscopusid9941747800
dc.contributor.authorscopusid50262281800
dc.contributor.authorscopusid8622097100
dc.contributor.authorscopusid36615462900
dc.contributor.authorscopusid6603722712
dc.contributor.authorscopusid7103160083
dc.contributor.authorscopusid7202545218
dc.contributor.authorscopusid7404864581
dc.contributor.authorscopusid50261885200
dc.contributor.authorscopusid26540762500
dc.contributor.authorscopusid57204346328
dc.contributor.authorscopusid7005810441
dc.contributor.authorscopusid6701341315
dc.contributor.authorscopusid7202675553
dc.contributor.authorscopusid56016515900
dc.description.lastpage69
dc.description.firstpage59
dc.relation.volume459
dc.type2Artículoes
dc.identifier.wosWOS:000333718700006
dc.contributor.daisngid846685
dc.contributor.daisngid4529981
dc.contributor.daisngid1473316
dc.contributor.daisngid5570384
dc.contributor.daisngid628983
dc.contributor.daisngid257621
dc.contributor.daisngid475608
dc.contributor.daisngid725270
dc.contributor.daisngid5154915
dc.contributor.daisngid29201
dc.contributor.daisngid90348
dc.contributor.daisngid231532
dc.contributor.daisngid39499
dc.contributor.daisngid31917458
dc.contributor.daisngid565477
dc.identifier.investigatorRIDC-6418-2016
dc.identifier.investigatorRIDB-5572-2015
dc.identifier.investigatorRIDE-2989-2012
dc.identifier.investigatorRIDNo ID
dc.identifier.investigatorRIDNo ID
dc.contributor.wosstandardWOS:Chaikuad, A
dc.contributor.wosstandardWOS:Keates, T
dc.contributor.wosstandardWOS:Vincke, C
dc.contributor.wosstandardWOS:Kaufholz, M
dc.contributor.wosstandardWOS:Zenn, M
dc.contributor.wosstandardWOS:Zimmermann, B
dc.contributor.wosstandardWOS:Gutierrez, C
dc.contributor.wosstandardWOS:Zhang, RG
dc.contributor.wosstandardWOS:Hatzos-Skintges, C
dc.contributor.wosstandardWOS:Joachimiak, A
dc.contributor.wosstandardWOS:Muyldermans, S
dc.contributor.wosstandardWOS:Herberg, FW
dc.contributor.wosstandardWOS:Knapp, S
dc.contributor.wosstandardWOS:Muller, S
dc.date.coverdateAbril 2014
dc.identifier.ulpgces
dc.description.sjr2,865
dc.description.jcr4,396
dc.description.sjrqQ1
dc.description.jcrqQ1
dc.description.scieSCIE
item.fulltextSin texto completo-
item.grantfulltextnone-
crisitem.author.deptGIR IUIBS: Medicina Veterinaria e Investigación Terapéutica-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.orcid0000-0003-0764-7408-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameGutiérrez Cabrera,Carlos Javier-
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