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The high-resolution crystal structure of phosphatidylinositol 4-kinase IIβ and the crystal structure of phosphatidylinositol 4-kinase IIα containing a nucleoside analogue provide a structural basis for isoform-specific inhibitor design

Authors :
Milan Dejmek
Evzen Boura
Martin Klima
Radim Nencka
Hubert Hřebabecký
Adriana Baumlova
Dominika Chalupska
Source :
Acta Crystallographica Section D Biological Crystallography. 71:1555-1563
Publication Year :
2015
Publisher :
International Union of Crystallography (IUCr), 2015.

Abstract

Phosphatidylinositol 4-phosphate (PI4P) is the most abundant monophosphoinositide in eukaryotic cells. Humans have four phosphatidylinositol 4-kinases (PI4Ks) that synthesize PI4P, among which are PI4K IIβ and PI4K IIα. In this study, two crystal structures are presented: the structure of human PI4K IIβ and the structure of PI4K IIα containing a nucleoside analogue. The former, a complex with ATP, is the first high-resolution (1.9 Å) structure of a PI4K. These structures reveal new details such as high conformational heterogeneity of the lateral hydrophobic pocket of the C-lobe and together provide a structural basis for isoform-specific inhibitor design.

Details

ISSN :
13990047
Volume :
71
Database :
OpenAIRE
Journal :
Acta Crystallographica Section D Biological Crystallography
Accession number :
edsair.doi.dedup.....80034882634d4aa4dc6420b0543da815