1IIG

STRUCTURE OF TRYPANOSOMA BRUCEI BRUCEI TRIOSEPHOSPHATE ISOMERASE COMPLEXED WITH 3-PHOSPHONOPROPIONATE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Observed: 0.125 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

The adaptability of the active site of trypanosomal triosephosphate isomerase as observed in the crystal structures of three different complexes.

Noble, M.E.Wierenga, R.K.Lambeir, A.M.Opperdoes, F.R.Thunnissen, A.M.Kalk, K.H.Groendijk, H.Hol, W.G.

(1991) Proteins 10: 50-69

  • DOI: https://doi.org/10.1002/prot.340100106
  • Primary Citation of Related Structures:  
    1IIG, 1IIH, 6TIM

  • PubMed Abstract: 

    Crystals of triosephosphate isomerase from Trypanosoma brucei brucei have been used in binding studies with three competitive inhibitors of the enzyme's activity. Highly refined structures have been deduced for the complexes between trypanosomal triosephosphate isomerase and a substrate analogue (glycerol-3-phosphate to 2.2 A), a transition state analogue (3-phosphonopropionic acid to 2.6 A), and a compound structurally related to both (3-phosphoglycerate to 2.2 A). The active site structures of these complexes were compared with each other, and with two previously determined structures of triosephosphate isomerase either free from inhibitor or complexed with sulfate. The comparison reveals three conformations available to the "flexible loop" near the active site of triosephosphate isomerase: open (no ligand), almost closed (sulfate), and fully closed (phosphate/phosphonate complexes). Also seen to be sensitive to the nature of the active site ligand is the catalytic residue Glu-167. The side chain of this residue occupies one of two discrete conformations in each of the structures so far observed. A "swung out" conformation unsuitable for catalysis is observed when sulfate, 3-phosphoglycerate, or no ligand is bound, while a "swung in" conformation ideal for catalysis is observed in the complexes with glycerol-3-phosphate or 3-phosphonopropionate. The water structure of the active site is different in all five structures. The results are discussed with respect to the triosephosphate isomerase structure function relationship, and with respect to an on-going drug design project aimed at the selective inhibition of glycolytic enzymes of T. brucei.


  • Organizational Affiliation

    European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TRIOSEPHOSPHATE ISOMERASE
A, B
250Trypanosoma brucei bruceiMutation(s): 0 
EC: 5.3.1.1
UniProt
Find proteins for P04789 (Trypanosoma brucei brucei)
Explore P04789 
Go to UniProtKB:  P04789
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04789
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
3PP
Query on 3PP

Download Ideal Coordinates CCD File 
C [auth B]3-PHOSPHONOPROPANOIC ACID
C3 H7 O5 P
NLBSQHGCGGFVJW-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
3PP PDBBind:  1IIG Ki: 2.70e+7 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Observed: 0.125 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 112.36α = 90
b = 97.59β = 90
c = 46.71γ = 90
Software Package:
Software NamePurpose
TNTrefinement
GROMOSrefinement
MADNESSdata reduction
BIOMOLdata scaling
TNTphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-05-11
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-04
    Changes: Refinement description
  • Version 1.4: 2018-04-18
    Changes: Data collection
  • Version 1.5: 2024-02-07
    Changes: Data collection, Database references, Derived calculations