Insight into the inhibition of human choline kinase: homology modeling and molecular dynamics simulations.
A homology model of human choline kinase (CK-alpha) based on the X-ray crystallographic structure of C. elegans choline kinase (CKA-2) is presented. Molecular dynamics simulations performed on CK-alpha confirm the quality of the model, and also support the putative ATP and choline binding sites. A good correlation between the MD results and reported CKA-2 mutagenesis assays has been found for the main residues involved in catalytic activity. Preliminary docking studies performed on the CK-alpha model indicate that inhibitors can bind to the binding sites of both substrates (ATP and choline). A possible reason for inhibition of choline kinase by Ca(2+) ion is also proposed.
Milanese
Lara
L
Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Campus de Cartuja s/n, Universidad de Granada, 18071 Granada, Spain.
Espinosa
Antonio
A
Campos
Joaquín M
JM
Gallo
Miguel A
MA
Entrena
Antonio
A
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology; D002797:Choline Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D002797:Choline Kinase