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Structure of GSK3 from Ustilago maydis
Structural highlights
Publication Abstract from PubMedProtein kinases are key enzymes in the complex regulation of cellular processes in almost all living organisms. For this reason, protein kinases represent attractive targets to stop the growth of eukaryotic pathogens such as protozoa and fungi. However, using kinase inhibitors to fight against these organisms bears several challenges since most of them are unselective and will also affect crucial host kinases. Here we present the X-ray structure of glycogen synthase kinase 3 from the fungal plant pathogen Ustilago maydis (<italic>Um</italic>GSK3) and its inhibition by type-II kinase inhibitors. Despite the high sequence homology between the human and the fungal variant of this vital kinase, we found substantial differences in the conformational plasticity of their active sites. Compounds that induced such conformational changes could be used to selectively inhibit the fungal kinase version. This study serves as an example how species specific selectivity of inhibitors can be achieved by identifying and addressing the inactive state of a protein kinase. In addition to this, our study gives interesting insights into the molecular plasticity of <italic>Um</italic>GSK3 by revealing a previously unknown inactive conformation of this important kinase family. Targeting GSK3 from <italic>Ustilago maydis</italic>: Type-II kinase inhibitors as potential antifungals.,Grutter C, Simard JR, Mayer-Wrangowski SC, Schreier PH, Perez-Martin J, Richters A, Getlik M, Gutbrod O, Braun CA, Beck ME, Rauh D ACS Chem Biol. 2012 Apr 30. PMID:22545924[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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