1TYP

SUBSTRATE INTERACTIONS BETWEEN TRYPANOTHIONE REDUCTASE AND N1-GLUTATHIONYLSPERMIDINE DISULPHIDE AT 0.28-NM RESOLUTION


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Work: 0.148 
  • R-Value Observed: 0.148 

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Literature

Substrate interactions between trypanothione reductase and N1-glutathionylspermidine disulphide at 0.28-nm resolution.

Bailey, S.Smith, K.Fairlamb, A.H.Hunter, W.N.

(1993) Eur J Biochem 213: 67-75

  • DOI: https://doi.org/10.1111/j.1432-1033.1993.tb17734.x
  • Primary Citation of Related Structures:  
    1TYP

  • PubMed Abstract: 

    The enzyme trypanothione reductase has been identified as a prime target for the rational design of inhibitors which may have clinical use in the treatment of tropical diseases caused by the genera Trypanosoma and Leishmania. To aid the design or identification of new inhibitors of this enzyme we have elucidated the structural detail of a trypanothione reductase complexed with one of the naturally occurring substrates, N1-glutathionylspermidine disulphide, by single-crystal X-ray diffraction methods at 0.28-nm resolution. The model for the Crithidia fasciculata enzyme-substrate complex has an R-factor of 14.8% and root-mean-square deviations of 0.0015 nm and 3.3 degrees on bond lengths and angles respectively. Hydrogen bonding and van der Waals interactions between the enzyme and substrate are dominated by the amino acid side chains. The substrate binds in a rigid active site such that one glutathione moiety is in a V-shape, the other in an extended conformation. One spermidine moiety binds closely to a hydrophobic patch in the active site formed by a tryptophan and a methionine. Distances between the methionine S delta and the terminal N of this spermidine suggest that a hydrogen bond may supplement the hydrophobic interactions in this part of the active site.


  • Organizational Affiliation

    Department of Chemistry, University of Manchester, England.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TRYPANOTHIONE REDUCTASE
A, B
487Crithidia fasciculataMutation(s): 0 
EC: 1.6.4.8 (PDB Primary Data), 1.8.1.12 (UniProt)
UniProt
Find proteins for P39040 (Crithidia fasciculata)
Explore P39040 
Go to UniProtKB:  P39040
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP39040
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FAD
Query on FAD

Download Ideal Coordinates CCD File 
C [auth A],
I [auth B]
FLAVIN-ADENINE DINUCLEOTIDE
C27 H33 N9 O15 P2
VWWQXMAJTJZDQX-UYBVJOGSSA-N
NAP
Query on NAP

Download Ideal Coordinates CCD File 
D [auth A],
J [auth B]
NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE
C21 H28 N7 O17 P3
XJLXINKUBYWONI-NNYOXOHSSA-N
GSH
Query on GSH

Download Ideal Coordinates CCD File 
E [auth A],
G [auth A],
K [auth B],
M [auth B]
GLUTATHIONE
C10 H17 N3 O6 S
RWSXRVCMGQZWBV-WDSKDSINSA-N
SPD
Query on SPD

Download Ideal Coordinates CCD File 
F [auth A],
H [auth A],
L [auth B],
N [auth B]
SPERMIDINE
C7 H19 N3
ATHGHQPFGPMSJY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Work: 0.148 
  • R-Value Observed: 0.148 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 128.8α = 90
b = 128.8β = 90
c = 92.5γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
X-PLORphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1994-01-31
    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: 2024-06-05
    Changes: Data collection, Database references, Derived calculations, Other