PDBsum entry 1e2n

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protein ligands Protein-protein interface(s) links
Transferase PDB id
Jmol PyMol
Protein chains
310 a.a. *
SO4 ×2
RCA ×2
Waters ×160
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Hpt + hmtt
Structure: Thymidine kinase. Chain: a, b. Engineered: yes
Source: Herpes simplex virus (type 1 / strain 17). Organism_taxid: 10299. Strain: 17. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Homo-Dimer (from PDB file)
2.20Å     R-factor:   0.208     R-free:   0.264
Authors: J.Vogt,L.Scapozza,G.E.Schulz
Key ref: C.Wurth et al. (2001). The effect of substrate binding on the conformation and structural stability of Herpes simplex virus type 1 thymidine kinase. Protein Sci, 10, 63-73. PubMed id: 11266595
23-May-00     Release date:   31-Mar-01    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P03176  (KITH_HHV11) -  Thymidine kinase
376 a.a.
310 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 = RCA)
matches with 58.00% similarity
+ thymidine 5'-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     TMP biosynthetic process   1 term 
  Biochemical function     ATP binding     2 terms  


Protein Sci 10:63-73 (2001)
PubMed id: 11266595  
The effect of substrate binding on the conformation and structural stability of Herpes simplex virus type 1 thymidine kinase.
C.Wurth, U.Kessler, J.Vogt, G.E.Schulz, G.Folkers, L.Scapozza.
The structure of Herpes simplex virus type 1 thymidine kinase (TK(HSV1)) is known at high resolution in complex with a series of ligands and exhibits important structural similarities to the nucleoside monophosphate (NMP) kinase family, which are known to show large conformational changes upon binding of substrates. The effect of substrate binding on the conformation and structural stability of TK(HSV1), measured by thermal denaturation experiments, far-UV circular dichroism (CD) and fluorescence is described, and the results indicate that the conformation of the ligand-free TK(HSV1) is less ordered and less stable compared to the ligated enzyme. Furthermore, two crystal structures of TK(HSV1) in complex with two new ligands, HPT and HMTT, refined to 2.2 A are presented. Although TK(HSV1):HPT does not exhibit any significant deviations from the model of TK(HSV1):dT, the TK(HSV1):HMTT complex displays a unique conformationally altered active site resulting in a lowered thermal stability of this complex. Moreover, we show that binding affinity and binding mode of the ligand correlate with thermal stability of the complex. We use this correlation to propose a method to estimate binding constants for new TK(HSV1)substrates using thermal denaturation measurements monitored by CD spectroscopy. The kinetic and structural results of both test substrates HPT and HMTT show that the CD thermal denaturation system is very sensitive to conformational changes caused by unusual binding of a substrate analog.

Literature references that cite this PDB file's key reference

  PubMed id Reference
18971333 C.Caillat, D.Topalis, L.A.Agrofoglio, S.Pochet, J.Balzarini, D.Deville-Bonne, and P.Meyer (2008).
Crystal structure of poxvirus thymidylate kinase: an unexpected dimerization has implications for antiviral therapy.
  Proc Natl Acad Sci U S A, 105, 16900-16905.
PDB codes: 2v54 2w0s
17623865 V.Ramensky, A.Sobol, N.Zaitseva, A.Rubinov, and V.Zosimov (2007).
A novel approach to local similarity of protein binding sites substantially improves computational drug design results.
  Proteins, 69, 349-357.  
16929558 P.Kapková, E.Heller, E.Kugelmann, J.Faber, G.Bringmann, U.Kessler, G.Folkers, and U.Holzgrabe (2006).
Random chemistry as a new tool for the generation of small-compound libraries.
  Arch Pharm (Weinheim), 339, 489-497.  
15340911 E.Kellenberger, J.Rodrigo, P.Muller, and D.Rognan (2004).
Comparative evaluation of eight docking tools for docking and virtual screening accuracy.
  Proteins, 57, 225-242.  
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