1KIM

CRYSTAL STRUCTURE OF THYMIDINE KINASE FROM HERPES SIMPLEX VIRUS TYPE I COMPLEXED WITH DEOXYTHYMIDINE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.14 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.209 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Exploring the active site of herpes simplex virus type-1 thymidine kinase by X-ray crystallography of complexes with aciclovir and other ligands.

Champness, J.N.Bennett, M.S.Wien, F.Visse, R.Summers, W.C.Herdewijn, P.de Clerq, E.Ostrowski, T.Jarvest, R.L.Sanderson, M.R.

(1998) Proteins 32: 350-361

  • DOI: https://doi.org/10.1002/(sici)1097-0134(19980815)32:3<350::aid-prot10>3.0.co;2-8
  • Primary Citation of Related Structures:  
    1KI2, 1KI3, 1KI4, 1KI6, 1KI7, 1KI8, 1KIM

  • PubMed Abstract: 

    Antiherpes therapies are principally targeted at viral thymidine kinases and utilize nucleoside analogs, the triphosphates of which are inhibitors of viral DNA polymerase or result in toxic effects when incorporated into DNA. The most frequently used drug, aciclovir (Zovirax), is a relatively poor substrate for thymidine kinase and high-resolution structural information on drugs and other molecules binding to the target is therefore important for the design of novel and more potent chemotherapy, both in antiherpes treatment and in gene therapy systems where thymidine kinase is expressed. Here, we report for the first time the binary complexes of HSV-1 thymidine kinase (TK) with the drug molecules aciclovir and penciclovir, determined by X-ray crystallography at 2.37 A resolution. Moreover, from new data at 2.14 A resolution, the refined structure of the complex of TK with its substrate deoxythymidine (R = 0.209 for 96% of all data) now reveals much detail concerning substrate and solvent interactions with the enzyme. Structures of the complexes of TK with four halogen-containing substrate analogs have also been solved, to resolutions better than 2.4 A. The various TK inhibitors broadly fall into three groups which together probe the space of the enzyme active site in a manner that no one molecule does alone, so giving a composite picture of active site interactions that can be exploited in the design of novel compounds.


  • Organizational Affiliation

    Division of Biomedical Sciences, Randall Institute, King's College, London, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
THYMIDINE KINASE
A, B
366Human alphaherpesvirus 1 strain 17Mutation(s): 0 
Gene Names: TK
EC: 2.7.1.21
UniProt
Find proteins for P0DTH5 (Human herpesvirus 1 (strain 17))
Explore P0DTH5 
Go to UniProtKB:  P0DTH5
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0DTH5
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
THM BindingDB:  1KIM IC50: 1000 (nM) from 1 assay(s)
-TΔS: min: 27.18, max: 50.09 (kJ/mol) from 4 assay(s)
ΔH: min: -7.99e+1, max: -5.71e+1 (kJ/mol) from 4 assay(s)
ΔG: min: -3.02e+1, max: -2.94e+1 (kJ/mol) from 3 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.14 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.209 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 113.4α = 90
b = 116.6β = 90
c = 108.2γ = 90
Software Package:
Software NamePurpose
SOLOMONphasing
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling
CCP4data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1998-05-20
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations