4E7W

Structure of GSK3 from Ustilago maydis

4E7W の概要

• エントリーDOI: 10.2210/pdb4e7w/pdb
• 分子名称: Glycogen Synthase Kinase 3 (1 entity in total)
• 機能のキーワード: gsk3, kinase, ptyr195, transferase
• 由来する生物種: Ustilago maydis (Smut fungus)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44797.78

構造登録者

Gruetter, C.,Rauh, D. (登録日: 2012-03-19, 公開日: 2012-05-16, 最終更新日: 2024-10-30)

主引用文献

Grutter, C.,Simard, J.R.,Mayer-Wrangowski, S.C.,Schreier, P.H.,Perez-Martin, J.,Richters, A.,Getlik, M.,Gutbrod, O.,Braun, C.A.,Beck, M.E.,Rauh, D.
Targeting GSK3 from Ustilago maydis: Type-II Kinase Inhibitors as Potential Antifungals.
Acs Chem.Biol., 7:1257-1267, 2012

PubMed Abstract: Protein 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 (UmGSK3) 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. This study serves as an example of 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 UmGSK3 by revealing a previously unknown inactive conformation of this important kinase family.

PubMed: 22545924
DOI: 10.1021/cb300128b

実験手法

X-RAY DIFFRACTION (3.3 Å)