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

被引：22

作者：

Klima, Martin ^{[1
]}

Baumlova, Adriana ^{[1
]}

Chalupska, Dominika ^{[1
]}

Hrebabecky, Hubert ^{[1
]}

Dejmek, Milan ^{[1
]}

Nencka, Radim ^{[1
]}

Boura, Evzen ^{[1
]}

机构：

[1] Acad Sci Czech Republ, Inst Organ Chem & Biochem, Dept Biochem, CR-16610 Prague, Czech Republic

来源：

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY | 2015年 / 71卷

关键词：

phosphatidyl inositol; kinase; crystal structure; ATP; inhibitor; PLASMA-MEMBRANE; TRAFFICKING; INSIGHTS; PROTEIN; RECRUITMENT; METABOLISM; REVEALS; COMPLEX; DOMAIN;

D O I：

10.1107/S1399004715009505

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1555 / 1563

页数：9

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