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

Klima Martin; Baumlova Adriana; Chalupska DominikaHrebabecky HubertDejmek MilanNencka RadimBoura Evzen

首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >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

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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

机译：高分辨率的晶体结构磷脂酰肌醇二4-kinaseβ和晶体结构的磷脂酰肌醇4-kinase IIα包含核苷模拟提供了结构基础isoform-specific抑制剂设计

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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.

机译：磷脂酰肌醇4-phosphate (PI4P)最丰富的monophosphoinositide真核生物细胞。4-kinases (PI4Ks)合成PI4P等PI4K IIβ和PI4K IIα。研究中,提出了两种晶体结构:人类PI4K IIβ结构和结构PI4K二世α包含核苷模拟。第一个高分辨率(1.9埃)的结构PI4K。构象异构性的横向C-lobe和疏水口袋一起提供了一个结构基础isoform-specific抑制剂的设计。

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《Acta crystallographica.Section D. Biological crystallography》 |2015年第7期|1555-1563|共9页
作者
Klima Martin; Baumlova Adriana; Chalupska DominikaHrebabecky HubertDejmek MilanNencka RadimBoura Evzen;
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Acad Sci Czech Republic, Inst Organ Chem & Biochem, Dept Biochem, CR-16610 Prague, Czech Republic;

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正文语种英语
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关键词
Kinase; 1-Phosphatidylinositol 4-Kinase; crystal structureoxetanocin APhosphatidylinositols;

机译：激酶;1-Phosphatidylinositol 4-Kinase;晶体structureoxetanocin APhosphatidylinositols;

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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

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