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PDBsum entry 2ja1

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protein ligands metals links
Transferase PDB id
2ja1
Jmol
Contents
Protein chain
193 a.a. *
Ligands
TTP
MPD
Metals
_ZN
Waters ×20
* Residue conservation analysis
PDB id:
2ja1
Name: Transferase
Title: Thymidine kinase from b. Cereus with ttp bound as phosphate donor.
Structure: Thymidine kinase. Chain: a. Engineered: yes
Source: Bacillus cereus. Organism_taxid: 1396. Strain: dvi. Variant: 98-7869. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.80Å     R-factor:   0.198     R-free:   0.239
Authors: U.Kosinska,C.Carnrot,M.P.B.Sandrini,A.R.Clausen,L.Wang,J.Pis S.Eriksson,H.Eklund
Key ref: U.Kosinska et al. (2007). Structural studies of thymidine kinases from Bacillus anthracis and Bacillus cereus provide insights into quaternary structure and conformational changes upon substrate binding. FEBS J, 274, 727-737. PubMed id: 17288553
Date:
17-Nov-06     Release date:   23-Jan-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q0H0H6  (Q0H0H6_BACCE) -  Thymidine kinase
Seq:
Struc:
195 a.a.
193 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.1.21  - Thymidine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + thymidine = ADP + thymidine 5'-phosphate
ATP
Bound ligand (Het Group name = TTP)
matches with 76.47% similarity
+ thymidine
= ADP
+ 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     7 terms  

 

 
    reference    
 
 
FEBS J 274:727-737 (2007)
PubMed id: 17288553  
 
 
Structural studies of thymidine kinases from Bacillus anthracis and Bacillus cereus provide insights into quaternary structure and conformational changes upon substrate binding.
U.Kosinska, C.Carnrot, M.P.Sandrini, A.R.Clausen, L.Wang, J.Piskur, S.Eriksson, H.Eklund.
 
  ABSTRACT  
 
Thymidine kinase (TK) is the key enzyme in salvaging thymidine to produce thymidine monophosphate. Owing to its ability to phosphorylate nucleoside analogue prodrugs, TK has gained attention as a rate-limiting drug activator. We describe the structures of two bacterial TKs, one from the pathogen Bacillus anthracis in complex with the substrate dT, and the second from the food-poison-associated Bacillus cereus in complex with the feedback inhibitor dTTP. Interestingly, in contrast with previous structures of TK in complex with dTTP, in this study dTTP occupies the phosphate donor site and not the phosphate acceptor site. This results in several conformational changes compared with TK structures described previously. One of the differences is the way tetramers are formed. Unlike B. anthracis TK, B. cereus TK shows a loose tetramer. Moreover, the lasso-domain is in open conformation in B. cereus TK without any substrate in the active site, whereas in B. anthracis TK the loop conformation is closed and thymidine occupies the active site. Another conformational difference lies within a region of 20 residues that we refer to as phosphate-binding beta-hairpin. The phosphate-binding beta-hairpin seems to be a flexible region of the enzyme which becomes ordered upon formation of hydrogen bonds to the alpha-phosphate of the phosphate donor, dTTP. In addition to descriptions of the different conformations that TK may adopt during the course of reaction, the oligomeric state of the enzyme is investigated.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20648496 J.Zander, M.Hartenfeller, V.Hähnke, E.Proschak, S.Besier, T.A.Wichelhaus, and G.Schneider (2010).
Multistep virtual screening for rapid and efficient identification of non-nucleoside bacterial thymidine kinase inhibitors.
  Chemistry, 16, 9630-9637.  
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.