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PDBsum entry 1p6x

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1p6x
Jmol
Contents
Protein chains
333 a.a. *
Ligands
SO4 ×6
THM ×2
Waters ×452
* Residue conservation analysis
PDB id:
1p6x
Name: Transferase
Title: Crystal structure of ehv4-tk complexed with thy and so4
Structure: Thymidine kinase. Chain: a, b. Engineered: yes
Source: Equid herpesvirus 4. Equine herpesvirus 4. Organism_taxid: 10331. Strain: 1942. Gene: tk. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.00Å     R-factor:   0.192     R-free:   0.237
Authors: A.Gardberg,L.Shuvalova,C.Monnerjahn,M.Konrad,A.Lavie
Key ref:
A.Gardberg et al. (2003). Structural basis for the dual thymidine and thymidylate kinase activity of herpes thymidine kinases. Structure, 11, 1265-1277. PubMed id: 14527394 DOI: 10.1016/j.str.2003.09.003
Date:
30-Apr-03     Release date:   04-Nov-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P24425  (KITH_EHV4) -  Thymidine kinase
Seq:
Struc:
352 a.a.
333 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.7.1.21  - Thymidine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + thymidine = ADP + thymidine 5'-phosphate
ATP
+
thymidine
Bound ligand (Het Group name = THM)
corresponds exactly
= ADP
+ thymidine 5'-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     phosphorylation   3 terms 
  Biochemical function     nucleotide binding     5 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.str.2003.09.003 Structure 11:1265-1277 (2003)
PubMed id: 14527394  
 
 
Structural basis for the dual thymidine and thymidylate kinase activity of herpes thymidine kinases.
A.Gardberg, L.Shuvalova, C.Monnerjahn, M.Konrad, A.Lavie.
 
  ABSTRACT  
 
Crystal structures of equine herpesvirus type-4 thymidine kinase (EHV4-TK) in complex with (i). thymidine and ADP, (ii). thymidine and SO(4) and the bisubstrate analogs, (iii). TP(4)A, and (iv). TP(5)A have been solved. Additionally, the structure of herpes simplex virus type-1 thymidine kinase (HSV1-TK) in complex with TP(5)A has been determined. These are the first structures of nucleoside kinases revealing conformational transitions upon binding of bisubstrate analogs. The structural basis for the dual thymidine and thymidylate kinase activity of these TKs is elucidated. While the active sites of HSV1-TK and EHV4-TK resemble one another, notable differences are observed in the Lid regions and in the way the enzymes bind the base of the phosphoryl-acceptor. The latter difference could partly explain the higher activity of EHV4-TK toward the prodrug ganciclovir.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Schematic Diagram Showing the Interactions Made by TP[4]A and TP[5]ADue to the all-open Lid conformations in the EHV4-TK TP[4]A and TP[5]A complex structures (but closed in the HSV1-TK structure), in (A) and (B) we modeled the closed-Lid conformation as observed in the EHV4-TK/ADP-Thy complex (simulated contacts shown in red and marked with an asterisk).(A) EHV4-TK complexed with TP[4]A. Owing to the 0.4 displacement of the b-phosphate, there is only one hydrogen bond to the P loop.(B) EHV4-TK complexed with TP[5]A, where only the mechanistically relevant conformation is shown.(C) HSV1-TK complexed with TP[5]A.
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 1265-1277) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  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.  
17977833 C.M.Van Itallie, L.Betts, J.G.Smedley, B.A.McClane, and J.M.Anderson (2008).
Structure of the claudin-binding domain of Clostridium perfringens enterotoxin.
  J Biol Chem, 283, 268-274.
PDB code: 2quo
18196203 I.T.Hussein, R.N.Miguel, L.S.Tiley, and H.J.Field (2008).
Substrate specificity and molecular modelling of the feline herpesvirus-1 thymidine kinase.
  Arch Virol, 153, 495-505.  
18715931 R.Sompallae, S.Gastaldello, S.Hildebrand, N.Zinin, G.Hassink, K.Lindsten, J.Haas, B.Persson, and M.G.Masucci (2008).
Epstein-barr virus encodes three bona fide ubiquitin-specific proteases.
  J Virol, 82, 10477-10486.  
18026086 K.A.Henzler-Wildman, V.Thai, M.Lei, M.Ott, M.Wolf-Watz, T.Fenn, E.Pozharski, M.A.Wilson, G.A.Petsko, M.Karplus, C.G.Hübner, and D.Kern (2007).
Intrinsic motions along an enzymatic reaction trajectory.
  Nature, 450, 838-844.
PDB codes: 2rgx 2rh5
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 code is shown on the right.