The structural basis for calcium inhibition of lipid kinase PI4K IIalpha and comparison with the apo state
Language English Country Czech Republic Media print-electronic
Document type Journal Article
PubMed
27539108
DOI
10.33549/physiolres.933344
PII: 933344
Knihovny.cz E-resources
- MeSH
- Adenosine Triphosphate metabolism MeSH
- Phosphatidylinositol Phosphates metabolism MeSH
- Phosphotransferases (Alcohol Group Acceptor) antagonists & inhibitors chemistry MeSH
- Catalytic Domain drug effects MeSH
- Protein Conformation MeSH
- Crystallography, X-Ray MeSH
- Models, Molecular MeSH
- trans-Golgi Network drug effects metabolism MeSH
- Calcium pharmacology MeSH
- Protein Binding MeSH
- Structure-Activity Relationship MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Adenosine Triphosphate MeSH
- Phosphatidylinositol Phosphates MeSH
- Phosphotransferases (Alcohol Group Acceptor) MeSH
- phosphatidylinositol 4-phosphate MeSH Browser
- PIP4K2A protein, human MeSH Browser
- Calcium MeSH
PI4K IIalpha is a critical enzyme for the maintenance of Golgi and is also known to function in the synaptic vesicles. The product of its catalytical function, phosphatidylinositol 4-phosphate (PI4P), is an important lipid molecule because it is a hallmark of the Golgi and TGN, is directly recognized by many proteins and also serves as a precursor molecule for synthesis of higher phosphoinositides. Here, we report crystal structures of PI4K IIalpha enzyme in the apo-state and inhibited by calcium. The apo-structure reveals a surprising rigidity of the active site residues important for catalytic activity. The structure of calcium inhibited kinase reveals how calcium locks ATP in the active site.
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