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PDBsum entry 2ckq

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protein ligands Protein-protein interface(s) links
Transferase PDB id
2ckq
Jmol
Contents
Protein chain
346 a.a. *
Ligands
_PC ×2
Waters ×109
* Residue conservation analysis
PDB id:
2ckq
Name: Transferase
Title: Crystal structure of human choline kinase alpha 2 in complex with phosphocholine
Structure: Choline kinase alpha. Chain: a, b. Fragment: splice isoform 2, residues 50-439. Synonym: ck, chetk-alpha, ethanolamine kinase, ek. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Dimer (from PDB file)
Resolution:
2.40Å     R-factor:   0.219     R-free:   0.259
Authors: E.Malito,A.Lavie
Key ref:
E.Malito et al. (2006). Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine. J Mol Biol, 364, 136-151. PubMed id: 17007874 DOI: 10.1016/j.jmb.2006.08.084
Date:
20-Apr-06     Release date:   04-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P35790  (CHKA_HUMAN) -  Choline kinase alpha
Seq:
Struc:
457 a.a.
347 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.2.7.1.32  - Choline kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + choline = ADP + phosphocholine
ATP
+ choline
= ADP
+
phosphocholine
Bound ligand (Het Group name = PC)
corresponds exactly
   Enzyme class 2: E.C.2.7.1.82  - Ethanolamine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + ethanolamine = ADP + O-phosphoethanolamine
ATP
+ ethanolamine
= ADP
+
O-phosphoethanolamine
Bound ligand (Het Group name = PC)
matches with 72.73% similarity
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     transferase activity, transferring phosphorus-containing groups     1 term  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2006.08.084 J Mol Biol 364:136-151 (2006)
PubMed id: 17007874  
 
 
Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine.
E.Malito, N.Sekulic, W.C.Too, M.Konrad, A.Lavie.
 
  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.
 
  Selected figure(s)  
 
Figure 1.
Figure 7.
Figure 7. Model of the ternary ADP-PChol complex. (a) Scheme showing H-bond interactions between hCKα2 residues and ADP or phosphocholine, as well as coordination of two Mg^2+, as black broken lines. (b) Stereo representation of the modeled ADP–PChol complex. This model was generated based on the closed hCK[PChol] structure, and analogy to APH(3′)-IIIa and cAPK. See the text for details.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 364, 136-151) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21035492 D.Gallego-Ortega, T.Gómez Del Pulgar, F.Valdés-Mora, A.Cebrián, and J.C.Lacal (2011).
Involvement of human choline kinase alpha and beta in carcinogenesis: A different role in lipid metabolism and biological functions.
  Adv Enzyme Regul, 51, 183-194.  
19855431 A.Yalcin, B.Clem, S.Makoni, A.Clem, K.Nelson, J.Thornburg, D.Siow, A.N.Lane, S.E.Brock, U.Goswami, J.W.Eaton, S.Telang, and J.Chesney (2010).
Selective inhibition of choline kinase simultaneously attenuates MAPK and PI3K/AKT signaling.
  Oncogene, 29, 139-149.  
19845508 B.Alberge, L.Gannoun-Zaki, C.Bascunana, C.Tran van Ba, H.Vial, and R.Cerdan (2010).
Comparison of the cellular and biochemical properties of Plasmodium falciparum choline and ethanolamine kinases.
  Biochem J, 425, 149-158.  
20299452 B.S.Hong, A.Allali-Hassani, W.Tempel, P.J.Finerty, F.Mackenzie, S.Dimov, M.Vedadi, and H.W.Park (2010).
Crystal structures of human choline kinase isoforms in complex with hemicholinium-3: single amino acid near the active site influences inhibitor sensitivity.
  J Biol Chem, 285, 16330-16340.
PDB codes: 3feg 3g15 3lq3
20089863 D.H.Fong, C.T.Lemke, J.Hwang, B.Xiong, and A.M.Berghuis (2010).
Structure of the antibiotic resistance factor spectinomycin phosphotransferase from Legionella pneumophila.
  J Biol Chem, 285, 9545-9555.
PDB codes: 3i0o 3i0q 3i1a
20077512 E.D.Scheeff, H.L.Axelrod, M.D.Miller, H.J.Chiu, A.M.Deacon, I.A.Wilson, and G.Manning (2010).
Genomics, evolution, and crystal structure of a new family of bacterial spore kinases.
  Proteins, 78, 1470-1482.
PDB code: 2q83
20822442 M.Morar, and G.D.Wright (2010).
The genomic enzymology of antibiotic resistance.
  Annu Rev Genet, 44, 25-51.  
20886003 W.C.Too, M.T.Wong, L.L.Few, and M.Konrad (2010).
Highly specific antibodies for co-detection of human choline kinase α1 and α2 isoforms.
  PLoS One, 5, e12999.  
19783652 J.Lee, J.Johnson, Z.Ding, M.Paetzel, and R.B.Cornell (2009).
Crystal structure of a mammalian CTP: phosphocholine cytidylyltransferase catalytic domain reveals novel active site residues within a highly conserved nucleotidyltransferase fold.
  J Biol Chem, 284, 33535-33548.
PDB code: 3hl4
18489261 F.Gibellini, W.N.Hunter, and T.K.Smith (2008).
Biochemical characterization of the initial steps of the Kennedy pathway in Trypanosoma brucei: the ethanolamine and choline kinases.
  Biochem J, 415, 135-144.  
17522047 S.Y.Ku, P.Yip, K.A.Cornell, M.K.Riscoe, J.B.Behr, G.Guillerm, and P.L.Howell (2007).
Structures of 5-methylthioribose kinase reveal substrate specificity and unusual mode of nucleotide binding.
  J Biol Chem, 282, 22195-22206.
PDB codes: 2pu8 2pui 2pul 2pun 2pup
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.