Please use this identifier to cite or link to this item:
http://hdl.handle.net/10553/51915
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chaikuad, Apirat | |
dc.contributor.author | Keates, Tracy | |
dc.contributor.author | Vincke, Cécile | |
dc.contributor.author | Kaufholz, Melanie | |
dc.contributor.author | Zenn, Michael | |
dc.contributor.author | Zimmermann, Bastian | |
dc.contributor.author | Gutierrez, Carlos | |
dc.contributor.author | Zhang, Rong Guang | |
dc.contributor.author | Hatzos-Skintges, Catherine | |
dc.contributor.author | Joachimiak, Andrzej | |
dc.contributor.author | Muyldermans, Serge | |
dc.contributor.author | Herberg, Friedrich W. | |
dc.contributor.author | Knapp, Stefan | |
dc.contributor.author | Müller, Susanne | |
dc.contributor.other | Muyldermans, Serge | |
dc.contributor.other | Herberg, Friedrich | |
dc.contributor.other | Gutierrez, Carlos | |
dc.contributor.other | Muller-Knapp, Susanne | |
dc.contributor.other | Knapp, Stefan | |
dc.date.accessioned | 2018-11-25T05:22:44Z | - |
dc.date.available | 2018-11-25T05:22:44Z | - |
dc.date.issued | 2014 | |
dc.identifier.issn | 0264-6021 | |
dc.identifier.uri | http://hdl.handle.net/10553/51915 | - |
dc.description.abstract | GAK (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.publisher | 0264-6021 | |
dc.relation.ispartof | Biochemical Journal | |
dc.source | Biochemical Journal[ISSN 0264-6021],v. 459, p. 59-69 | |
dc.subject.other | Clathrin | |
dc.subject.other | Receptor | |
dc.subject.other | Domain | |
dc.subject.other | Refinement | |
dc.subject.other | Proteins | |
dc.subject.other | Complex | |
dc.subject.other | Tools | |
dc.title | Structure of cyclin G-associated kinase (GAK) trapped in different conformations using nanobodies | |
dc.type | info:eu-repo/semantics/Article | es |
dc.type | Article | es |
dc.identifier.doi | 10.1042/BJ20131399 | |
dc.identifier.scopus | 84896138811 | |
dc.identifier.isi | 000333718700006 | |
dcterms.isPartOf | Biochemical Journal | |
dcterms.source | Biochemical Journal[ISSN 0264-6021],v. 459, p. 59-69 | |
dc.contributor.authorscopusid | 9941747800 | |
dc.contributor.authorscopusid | 50262281800 | |
dc.contributor.authorscopusid | 8622097100 | |
dc.contributor.authorscopusid | 36615462900 | |
dc.contributor.authorscopusid | 6603722712 | |
dc.contributor.authorscopusid | 7103160083 | |
dc.contributor.authorscopusid | 7202545218 | |
dc.contributor.authorscopusid | 7404864581 | |
dc.contributor.authorscopusid | 50261885200 | |
dc.contributor.authorscopusid | 26540762500 | |
dc.contributor.authorscopusid | 57204346328 | |
dc.contributor.authorscopusid | 7005810441 | |
dc.contributor.authorscopusid | 6701341315 | |
dc.contributor.authorscopusid | 7202675553 | |
dc.contributor.authorscopusid | 56016515900 | |
dc.description.lastpage | 69 | |
dc.description.firstpage | 59 | |
dc.relation.volume | 459 | |
dc.type2 | Artículo | es |
dc.identifier.wos | WOS:000333718700006 | |
dc.contributor.daisngid | 846685 | |
dc.contributor.daisngid | 4529981 | |
dc.contributor.daisngid | 1473316 | |
dc.contributor.daisngid | 5570384 | |
dc.contributor.daisngid | 628983 | |
dc.contributor.daisngid | 257621 | |
dc.contributor.daisngid | 475608 | |
dc.contributor.daisngid | 725270 | |
dc.contributor.daisngid | 5154915 | |
dc.contributor.daisngid | 29201 | |
dc.contributor.daisngid | 90348 | |
dc.contributor.daisngid | 231532 | |
dc.contributor.daisngid | 39499 | |
dc.contributor.daisngid | 31917458 | |
dc.contributor.daisngid | 565477 | |
dc.identifier.investigatorRID | C-6418-2016 | |
dc.identifier.investigatorRID | B-5572-2015 | |
dc.identifier.investigatorRID | E-2989-2012 | |
dc.identifier.investigatorRID | No ID | |
dc.identifier.investigatorRID | No ID | |
dc.contributor.wosstandard | WOS:Chaikuad, A | |
dc.contributor.wosstandard | WOS:Keates, T | |
dc.contributor.wosstandard | WOS:Vincke, C | |
dc.contributor.wosstandard | WOS:Kaufholz, M | |
dc.contributor.wosstandard | WOS:Zenn, M | |
dc.contributor.wosstandard | WOS:Zimmermann, B | |
dc.contributor.wosstandard | WOS:Gutierrez, C | |
dc.contributor.wosstandard | WOS:Zhang, RG | |
dc.contributor.wosstandard | WOS:Hatzos-Skintges, C | |
dc.contributor.wosstandard | WOS:Joachimiak, A | |
dc.contributor.wosstandard | WOS:Muyldermans, S | |
dc.contributor.wosstandard | WOS:Herberg, FW | |
dc.contributor.wosstandard | WOS:Knapp, S | |
dc.contributor.wosstandard | WOS:Muller, S | |
dc.date.coverdate | Abril 2014 | |
dc.identifier.ulpgc | Sí | es |
dc.description.sjr | 2,865 | |
dc.description.jcr | 4,396 | |
dc.description.sjrq | Q1 | |
dc.description.jcrq | Q1 | |
dc.description.scie | SCIE | |
item.fulltext | Sin texto completo | - |
item.grantfulltext | none | - |
crisitem.author.dept | GIR IUIBS: Medicina Veterinaria e Investigación Terapéutica | - |
crisitem.author.dept | IU de Investigaciones Biomédicas y Sanitarias | - |
crisitem.author.orcid | 0000-0003-0764-7408 | - |
crisitem.author.parentorg | IU de Investigaciones Biomédicas y Sanitarias | - |
crisitem.author.fullName | Gutiérrez Cabrera,Carlos Javier | - |
Appears in Collections: | Artículos |
SCOPUSTM
Citations
48
checked on Oct 6, 2024
WEB OF SCIENCETM
Citations
46
checked on Oct 6, 2024
Page view(s)
36
checked on Jun 8, 2024
Google ScholarTM
Check
Altmetric
Share
Export metadata
Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.