PDBsum entry 2orw

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Protein chains
171 a.a. *
4TA ×2
_MG ×2
_ZN ×2
Waters ×370
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Thermotoga maritima thymidine kinase 1 like enzyme in complex with tp4a
Structure: Thymidine kinase. Chain: a, b. Engineered: yes
Source: Thermotoga maritima. Organism_taxid: 2336. Gene: tdk. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.50Å     R-factor:   0.173     R-free:   0.208
Authors: D.Segura-Pena,S.Lutz,C.Monnerjahn,M.Konrad,A.Lavie
Key ref:
D.Segura-Peña et al. (2007). Binding of ATP to TK1-like Enzymes Is Associated with a Conformational Change in the Quaternary Structure. J Mol Biol, 369, 129-141. PubMed id: 17407781 DOI: 10.1016/j.jmb.2007.02.104
04-Feb-07     Release date:   27-Mar-07    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q9WYN2  (KITH_THEMA) -  Thymidine kinase
184 a.a.
171 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Thymidine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + thymidine = ADP + thymidine 5'-phosphate
Bound ligand (Het Group name = 4TA)
matches with 60.00% similarity
+ thymidine
+ thymidine 5'-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     DNA metabolic process   4 terms 
  Biochemical function     nucleotide binding     6 terms  


DOI no: 10.1016/j.jmb.2007.02.104 J Mol Biol 369:129-141 (2007)
PubMed id: 17407781  
Binding of ATP to TK1-like Enzymes Is Associated with a Conformational Change in the Quaternary Structure.
D.Segura-Peña, S.Lutz, C.Monnerjahn, M.Konrad, A.Lavie.
Human thymidine kinase 1 (hTK1) and structurally related TKs from other organisms catalyze the initial phosphorylation step in the thymidine salvage pathway. Though ATP is known to be the preferred phosphoryl donor for TK1-like enzymes, its exact binding mode and effect on the oligomeric state has not been analyzed. Here we report the structures of hTK1 and of the Thermotoga maritima thymidine kinase (TmTK) in complex with the bisubstrate inhibitor TP4A. The TmTK-TP4A structure reveals that the adenosine moiety of ATP binds at the subunit interface of the homotetrameric enzyme and that the majority of the ATP-enzyme interactions occur between the phosphate groups and the P-loop. In the hTK1 structure the adenosine group of TP4A exhibited no electron density. This difference between hTK1 and TmTK is rationalized by a difference in the conformation of their quaternary structure. A more open conformation, as seen in the TmTK-TP4A complex structure, is required to provide space for the adenosine moiety. Our analysis supports the formation of an analogous open conformation in hTK1 upon ATP binding.
  Selected figure(s)  
Figure 4.
Figure 4. The thymidine-binding site. Stereo views of the thymidine moiety of TP4A (green) bound to (a) hTK1 and (b) TmTK. A special feature of TK1-like kinases is the involvement of main chain atoms in binding the thymine base (hydrogen bonds between the nucleoside and the enzyme are depicted as broken lines). The putative role of the conserved carboxylic acid, Glu98 in hTK1 and Glu84 in TmTK, is to activate the thymidine 5′-hydroxyl for nucleophilic attack on the ATP γ-phosphate.
Figure 5.
Figure 5. The ATP binding site in TmTK. (a) Stereo view of TP4A bound to TmTK. The phosphate groups bind to the enzyme P-loop (residues 10–16). We observe an octahedrally liganded magnesium atom. The conserved carboxylic acid residues at positions 83 and 84 interact via water molecules with the magnesium. (b) The adenosine moiety is sandwiched between two monomers that make up dimers of type II. The base is flanked by Tyr13 of one monomer and Leu29 of another. Glu25 of the neighboring subunit also directly interacts with the adenosine ribose moiety.
  The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2007, 369, 129-141) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21339943 X.Wang, M.Wiens, M.Divekar, V.A.Grebenjuk, H.C.Schröder, R.Batel, and W.E.Müller (2010).
Isolation and Characterization of a Mn(II)-Oxidizing Bacillus Strain from the Demosponge Suberites domuncula.
  Mar Drugs, 9, 1.  
19087190 B.Munch-Petersen (2009).
Reversible tetramerization of human TK1 to the high catalytic efficient form is induced by pyrophosphate, in addition to tripolyphosphates, or high enzyme concentration.
  FEBS J, 276, 571-580.  
19474348 L.Liu, Y.Li, D.Liotta, and S.Lutz (2009).
Directed evolution of an orthogonal nucleoside analog kinase via fluorescence-activated cell sorting.
  Nucleic Acids Res, 37, 4472-4481.  
20119480 P.Lupieri, C.H.Nguyen, Z.G.Bafghi, A.Giorgetti, and P.Carloni (2009).
Computational molecular biology approaches to ligand-target interactions.
  HFSP J, 3, 228-239.  
  20305804 S.Lutz, L.Liu, and Y.Liu (2009).
Engineering Kinases to Phosphorylate Nucleoside Analogs for Antiviral and Cancer Therapy.
  Chimia (Aarau), 63, 737-744.  
18073106 D.Segura-Peña, J.Lichter, M.Trani, M.Konrad, A.Lavie, and S.Lutz (2007).
Quaternary structure change as a mechanism for the regulation of thymidine kinase 1-like enzymes.
  Structure, 15, 1555-1566.
PDB codes: 2qpo 2qq0 2qqe
17592850 S.Lutz, J.Lichter, and L.Liu (2007).
Exploiting temperature-dependent substrate promiscuity for nucleoside analogue activation by thymidine kinase from Thermotoga maritima.
  J Am Chem Soc, 129, 8714-8715.  
18049729 W.Tjarks, R.Tiwari, Y.Byun, S.Narayanasamy, and R.F.Barth (2007).
Carboranyl thymidine analogues for neutron capture therapy.
  Chem Commun (Camb), (), 4978-4991.  
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.