1W0C

Inhibition of Leishmania major pteridine reductase (PTR1) by 2,4,6-triaminoquinazoline; structure of the NADP ternary complex.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.337 
  • R-Value Work: 0.267 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Inhibition of Leishmania Major Pteridine Reductase by 2,4,6-Triaminoquinazoline: Structure of the Nadph Ternary Complex

Mcluskey, K.Gibellini, F.Carvalho, P.Avery, M.Hunter, W.

(2004) Acta Crystallogr D Biol Crystallogr 60: 1780

  • DOI: https://doi.org/10.1107/S0907444904018955
  • Primary Citation of Related Structures:  
    1W0C

  • PubMed Abstract: 

    The structure of Leishmania major pteridine reductase (PTR1) in complex with NADPH and the inhibitor 2,4,6-triaminoquinazoline (TAQ) has been solved in a new crystal form by molecular replacement and refined to 2.6 A resolution. The inhibitor mimics a fragment, the pterin head group, of the archetypal antifolate drug methotrexate (MTX) and exploits similar chemical features to bind in the PTR1 active site. Despite being a much smaller molecule, TAQ displays a similar inhibition constant to that of MTX. PTR1 is a target for the development of improved therapies for infections caused by trypanosomatid parasites and this analysis provides information to assist the structure-based development of novel enzyme inhibitors.


  • Organizational Affiliation

    Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PTERIDINE REDUCTASE
A, B, C, D, E
A, B, C, D, E, F, G, H
307Leishmania majorMutation(s): 0 
EC: 1.5.1.33
UniProt
Find proteins for Q01782 (Leishmania major)
Explore Q01782 
Go to UniProtKB:  Q01782
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ01782
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAP
Query on NAP

Download Ideal Coordinates CCD File 
I [auth A]
L [auth B]
N [auth C]
P [auth D]
R [auth E]
I [auth A],
L [auth B],
N [auth C],
P [auth D],
R [auth E],
T [auth F],
V [auth G],
X [auth H]
NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
TAQ
Query on TAQ

Download Ideal Coordinates CCD File 
J [auth A]
K [auth A]
M [auth B]
O [auth C]
Q [auth D]
J [auth A],
K [auth A],
M [auth B],
O [auth C],
Q [auth D],
S [auth E],
U [auth F],
W [auth G],
Y [auth H]
2,4,6-TRIAMINOQUINAZOLINE
C8 H9 N5
LJBWEZVYRBKOCI-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
TAQ BindingDB:  1W0C Kd: 5.88e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.337 
  • R-Value Work: 0.267 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 95.851α = 90
b = 102.945β = 108.32
c = 146.707γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-09-30
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description