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Fluorophore labeled kinase detects ligands that bind within the MAPK insert of p38α kinase

dc.contributor.authorGetlik, Matthausen_ZA
dc.contributor.authorSimard, Jeffrey R.en_ZA
dc.contributor.authorTermathe, Martinen_ZA
dc.contributor.authorGrutter, Christianen_ZA
dc.contributor.authorRabiller, Matthiasen_ZA
dc.contributor.authorVan Otterlo, Willem A. L.en_ZA
dc.contributor.authorRauh, Danielen_ZA
dc.date.accessioned2012-07-26T07:16:17Z
dc.date.available2012-07-26T07:16:17Z
dc.date.issued2012-07-02
dc.identifier.citationGetlik, M. et al. 2012. Fluorophore labeled kinase detects ligands that bind within the MAPK insert of p38α kinase. PLoS ONE, 7(7): e39713, doi:10.1371/journal.pone.0039713.
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0039713
dc.identifier.urihttp://hdl.handle.net/10019.1/21827
dc.descriptionCITATION: Getlik, M. et al. 2012. Fluorophore labeled kinase detects ligands that bind within the MAPK insert of p38α kinase. PLoS ONE, 7(7): e39713, doi:10.1371/journal.pone.0039713.
dc.descriptionThe original publication is available at http://journals.plos.org/plosone
dc.description.abstractENGLISH ABSTRACT: The vast majority of small molecules known to modulate kinase activity, target the highly conserved ATP-pocket. Consequently, such ligands are often less specific and in case of inhibitors, this leads to the inhibition of multiple kinases. Thus, selective modulation of kinase function remains a major hurdle. One of the next great challenges in kinase research is the identification of ligands which bind to less conserved sites and target the non-catalytic functions of protein kinases. However, approaches that allow for the unambiguous identification of molecules that bind to these less conserved sites are few in number. We have previously reported the use of fluorescent labels in kinases (FLiK) to develop direct kinase binding assays that exclusively detect ligands which stabilize inactive (DFG-out) kinase conformations. Here, we present the successful application of the FLiK approach to develop a high-throughput binding assay capable of directly monitoring ligand binding to a remote site within the MAPK insert of p38α mitogen-activated protein kinase (MAPK). Guided by the crystal structure of an initially identified hit molecule in complex with p38α, we developed a tight binding ligand which may serve as an ideal starting point for further investigations of the biological function of the MAPK insert in regulating the p38α signaling pathway. © 2012 Getlik et al.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Geen opsomming beskikbaaraf_ZA
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039713
dc.format.extent10 pagesen_ZA
dc.language.isoen_ZAen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.subjectProtein kinasesen_ZA
dc.subjectLigandsen_ZA
dc.subjectFluorometryen_ZA
dc.titleFluorophore labeled kinase detects ligands that bind within the MAPK insert of p38α kinaseen_ZA
dc.typeArticleen_ZA
dc.description.versionPublisher's version
dc.rights.holderAuthors retain copyrighten_ZA


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