2CKP

Crystal structure of Human Choline Kinase alpha-2 in complex with ADP

Summary for 2CKP

• Entry DOI: 10.2210/pdb2ckp/pdb
• Related: 2CKO 2CKQ
• Descriptor: CHOLINE KINASE ALPHA, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: kinase, transferase, choline kinase, phosphatydilcholine
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: P35790
• Total number of polymer chains: 2
• Total formula weight: 91179.73

Authors

Malito, E.,Lavie, A. (deposition date: 2006-04-20, release date: 2006-10-04, Last modification date: 2023-12-13)

Primary citation

Malito, E.,Sekulic, N.,Too, W.C.,Konrad, M.,Lavie, A.
Elucidation of Human Choline Kinase Crystal Structures in Complex with the Products Adp or Phosphocholine.
J.Mol.Biol., 364:136-, 2006

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.

PubMed: 17007874
DOI: 10.1016/J.JMB.2006.08.084

Experimental method

X-RAY DIFFRACTION (3.1 Å)