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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
- 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.
- Subjects :
- Gene isoform
Protein Conformation
High resolution
Crystal structure
Crystallography, X-Ray
chemistry.chemical_compound
Adenosine Triphosphate
Structural Biology
Catalytic Domain
medicine
Humans
Protein Isoforms
Transferase
Phosphatidylinositol
1-Phosphatidylinositol 4-Kinase
Protein Kinase Inhibitors
Nucleoside analogue
Kinase
Chemistry
Phosphatidyl inositol
Nucleosides
General Medicine
Biochemistry
Drug Design
Hydrophobic and Hydrophilic Interactions
medicine.drug
Subjects
Details
- ISSN :
- 13990047
- Volume :
- 71
- Database :
- OpenAIRE
- Journal :
- Acta Crystallographica Section D Biological Crystallography
- Accession number :
- edsair.doi.dedup.....80034882634d4aa4dc6420b0543da815