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

0446387 - ÚOCHB 2016 RIV DK eng J - Článek v odborném periodiku
Klíma, Martin - Bäumlová, Adriana - Chalupská, Dominika - Hřebabecký, Hubert - Dejmek, Milan - Nencka, Radim - Bouřa, Evžen
The high-resolution crystal structure of phosphatidylinositol 4-kinase II beta and the crystal structure of phosphatidylinositol 4-kinase II alpha containing a nucleoside analogue provide a structural basis for isoform-specific inhibitor design.
Acta Crystallographica Section D-Biological Crystallography. Roč. 71, č. 7 (2015), s. 1555-1563. ISSN 1399-0047. E-ISSN 2059-7983
Grant CEP: GA ČR GJ15-21030Y; GA ČR GA15-09310S; GA MŠMT LO1302
GRANT EU: European Commission(XE) 333916 - STARPI4K
Institucionální podpora: RVO:61388963
Klíčová slova: phosphatidyl inositol * kinase * crystal structure * ATP * inhibitor
Kód oboru RIV: CE - Biochemie
Impakt faktor: 2.512, rok: 2015

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 II beta and PI4K II alpha. In this study, two crystal structures are presented: the structure of human PI4K II beta and the structure of PI4K II alpha containing a nucleoside analogue. The former, a complex with ATP, is the first high-resolution (1.9 angstrom) 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.
Trvalý link: http://hdl.handle.net/11104/0248456