Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine.
Article Details
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Malito E, Sekulic N, Too WC, Konrad M, Lavie A
Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine.
J Mol Biol. 2006 Nov 24;364(2):136-51. Epub 2006 Sep 3.
- PubMed ID
- 17007874 [ View in PubMed]
- Abstract
Choline kinase, responsible for the phosphorylation of choline to phosphocholine as the first step of the CDP-choline pathway for the biosynthesis of phosphatidylcholine, has been recognized as a new target for anticancer therapy. Crystal structures of human choline kinase in its apo, ADP and phosphocholine-bound complexes, respectively, reveal the molecular details of the substrate binding sites. ATP binds in a cavity where residues from both the N and C-terminal lobes contribute to form a cleft, while the choline-binding site constitutes a deep hydrophobic groove in the C-terminal domain with a rim composed of negatively charged residues. Upon binding of choline, the enzyme undergoes conformational changes independently affecting the N-terminal domain and the ATP-binding loop. From this structural analysis and comparison with other kinases, and from mutagenesis data on the homologous Caenorhabditis elegans choline kinase, a model of the ternary ADP.phosphocholine complex was built that reveals the molecular basis for the phosphoryl transfer activity of this enzyme.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Choline Choline kinase alpha Protein Humans UnknownSubstrateDetails Choline salicylate Choline kinase alpha Protein Humans UnknownSubstrateDetails - Polypeptides
Name UniProt ID Choline kinase alpha P35790 Details