PDBsum entry 3lq3

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protein ligands metals links
Transferase PDB id
Jmol PyMol
Protein chain
339 a.a. *
UNX ×2
Waters ×275
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of human choline kinase beta in complex wi phosphorylated hemicholinium-3 and adenosine nucleotide
Structure: Choline/ethanolamine kinase. Chain: a. Synonym: choline/ethanolamine kinase beta, ckekb, choline k beta, ckb, ck, choline kinase-like protein, ethanolamine ki ethanolamine kinase beta, ekb. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: chkb, chetk, chkl. Expressed in: escherichia coli. Expression_system_taxid: 469008.
1.42Å     R-factor:   0.188     R-free:   0.213
Authors: B.S.Hong,W.Tempel,W.M.Rabeh,F.Mackenzie,C.H.Arrowsmith,A.M.E C.Bountra,J.Weigelt,A.Bochkarev,H.W.Park,Structural Genomic Consortium (Sgc)
Key ref: B.S.Hong et al. (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. PubMed id: 20299452
08-Feb-10     Release date:   05-May-10    
Go to PROCHECK summary

Protein chain
-  (POLG_HAVHM) - 
Protein chain
Pfam   ArchSchema ?
Q9Y259  (CHKB_HUMAN) -  Choline/ethanolamine kinase
395 a.a.
339 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.  - Choline kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + choline = ADP + phosphocholine
+ choline
Bound ligand (Het Group name = ADP)
corresponds exactly
+ phosphocholine
   Enzyme class 2: E.C.  - Ethanolamine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + ethanolamine = ADP + O-phosphoethanolamine
+ ethanolamine
Bound ligand (Het Group name = ADP)
corresponds exactly
+ O-phosphoethanolamine
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!
  Cellular component     cytosol   1 term 
  Biological process     lipid metabolic process   7 terms 
  Biochemical function     nucleotide binding     6 terms  


J Biol Chem 285:16330-16340 (2010)
PubMed id: 20299452  
Crystal structures of human choline kinase isoforms in complex with hemicholinium-3: single amino acid near the active site influences inhibitor sensitivity.
B.S.Hong, A.Allali-Hassani, W.Tempel, P.J.Finerty, F.Mackenzie, S.Dimov, M.Vedadi, H.W.Park.
Human choline kinase (ChoK) catalyzes the first reaction in phosphatidylcholine biosynthesis and exists as ChoKalpha (alpha1 and alpha2) and ChoKbeta isoforms. Recent studies suggest that ChoK is implicated in tumorigenesis and emerging as an attractive target for anticancer chemotherapy. To extend our understanding of the molecular mechanism of ChoK inhibition, we have determined the high resolution x-ray structures of the ChoKalpha1 and ChoKbeta isoforms in complex with hemicholinium-3 (HC-3), a known inhibitor of ChoK. In both structures, HC-3 bound at the conserved hydrophobic groove on the C-terminal lobe. One of the HC-3 oxazinium rings complexed with ChoKalpha1 occupied the choline-binding pocket, providing a structural explanation for its inhibitory action. Interestingly, the HC-3 molecule co-crystallized with ChoKbeta was phosphorylated in the choline binding site. This phosphorylation, albeit occurring at a very slow rate, was confirmed experimentally by mass spectroscopy and radioactive assays. Detailed kinetic studies revealed that HC-3 is a much more potent inhibitor for ChoKalpha isoforms (alpha1 and alpha2) compared with ChoKbeta. Mutational studies based on the structures of both inhibitor-bound ChoK complexes demonstrated that Leu-401 of ChoKalpha2 (equivalent to Leu-419 of ChoKalpha1), or the corresponding residue Phe-352 of ChoKbeta, which is one of the hydrophobic residues neighboring the active site, influences the plasticity of the HC-3-binding groove, thereby playing a key role in HC-3 sensitivity and phosphorylation.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21035492 D.Gallego-Ortega, T.G.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.  
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