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
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26143926
DOI
10.1107/s1399004715009505
PII: S1399004715009505
Knihovny.cz E-resources
- Keywords
- ATP, crystal structure, inhibitor, kinase, phosphatidyl inositol,
- MeSH
- 1-Phosphatidylinositol 4-Kinase antagonists & inhibitors chemistry metabolism MeSH
- Adenosine Triphosphate metabolism MeSH
- Hydrophobic and Hydrophilic Interactions MeSH
- Protein Kinase Inhibitors chemistry pharmacology MeSH
- Catalytic Domain MeSH
- Protein Conformation MeSH
- Crystallography, X-Ray MeSH
- Humans MeSH
- Nucleosides chemistry pharmacology MeSH
- Protein Isoforms antagonists & inhibitors chemistry metabolism MeSH
- Drug Design * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 1-Phosphatidylinositol 4-Kinase MeSH
- Adenosine Triphosphate MeSH
- Protein Kinase Inhibitors MeSH
- Nucleosides MeSH
- Protein Isoforms MeSH
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.
References provided by Crossref.org
Purine analogs as phosphatidylinositol 4-kinase IIIβ inhibitors
