1LIO

STRUCTURE OF APO T. GONDII ADENOSINE KINASE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.200 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.

Schumacher, M.A.Scott, D.M.Mathews, I.I.Ealick, S.E.Roos, D.S.Ullman, B.Brennan, R.G.

(2000) J Mol Biol 298: 875-893

  • DOI: https://doi.org/10.1006/jmbi.2000.3753
  • Primary Citation of Related Structures:  
    1LII, 1LIJ, 1LIK, 1LIO

  • PubMed Abstract: 

    Adenosine kinase (AK) is a key purine metabolic enzyme from the opportunistic parasitic protozoan Toxoplasma gondii and belongs to the family of carbohydrate kinases that includes ribokinase. To understand the catalytic mechanism of AK, we determined the structures of the T. gondii apo AK, AK:adenosine complex and the AK:adenosine:AMP-PCP complex to 2.55 A, 2.50 A and 1.71 A resolution, respectively. These structures reveal a novel catalytic mechanism that involves an adenosine-induced domain rotation of 30 degrees and a newly described anion hole (DTXGAGD), requiring a helix-to-coil conformational change that is induced by ATP binding. Nucleotide binding also evokes a coil-to-helix transition that completes the formation of the ATP binding pocket. A conserved dipeptide, Gly68-Gly69, which is located at the bottom of the adenosine-binding site, functions as the switch for domain rotation. The synergistic structural changes that occur upon substrate binding sequester the adenosine and the ATP gamma phosphate from solvent and optimally position the substrates for catalysis. Finally, the 1.84 A resolution structure of an AK:7-iodotubercidin:AMP-PCP complex reveals the basis for the higher affinity binding of this prodrug over adenosine and thus provides a scaffold for the design of new inhibitors and subversive substrates that target the T. gondii AK.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology, Vollum Institute, Oregon Health Sciences University, Portland 97201-3098, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
adenosine kinase363Toxoplasma gondiiMutation(s): 0 
EC: 2.7.1.20
UniProt
Find proteins for Q9TVW2 (Toxoplasma gondii)
Explore Q9TVW2 
Go to UniProtKB:  Q9TVW2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9TVW2
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.198 
  • R-Value Observed: 0.200 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.1α = 90
b = 68β = 100.8
c = 56.8γ = 90
Software Package:
Software NamePurpose
MERLOTphasing
TNTrefinement
bioteXdata reduction
bioteXdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-06-12
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references