title: The structural basis for calcium inhibition of lipid kinase PI4K IIalpha and comparison with the apo state.
abstract: 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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic. boura@uochb.cas.cz.
authors.forename: A
authors.initials: A
authors.lastname: Baumlova
authors.forename: J
authors.initials: J
authors.lastname: Gregor
authors.forename: E
authors.initials: E
authors.lastname: Boura
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D020134:Catalytic Domain / Q000187:drug effects; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D021601:trans-Golgi Network / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018129:Phosphatidylinositol Phosphates; C037178:phosphatidylinositol 4-phosphate; D000255:Adenosine Triphosphate; C514871:PIP4K2A protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); D002118:Calcium