5B1S

Crystal structure of Trypanosoma cruzi spermidine synthase in complex with 2-(2-fluorophenyl)ethanamine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.58 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.188 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

In silico, in vitro, X-ray crystallography, and integrated strategies for discovering spermidine synthase inhibitors for Chagas disease

Yoshino, R.Yasuo, N.Hagiwara, Y.Ishida, T.Inaoka, D.K.Amano, Y.Tateishi, Y.Ohno, K.Namatame, I.Niimi, T.Orita, M.Kita, K.Akiyama, Y.Sekijima, M.

(2017) Sci Rep 7: 6666-6666

  • DOI: https://doi.org/10.1038/s41598-017-06411-9
  • Primary Citation of Related Structures:  
    5B1S

  • PubMed Abstract: 

    Chagas disease results from infection by Trypanosoma cruzi and is a neglected tropical disease (NTD). Although some treatment drugs are available, their use is associated with severe problems, including adverse effects and limited effectiveness during the chronic disease phase. To develop a novel anti-Chagas drug, we virtually screened 4.8 million small molecules against spermidine synthase (SpdSyn) as the target protein using our super computer "TSUBAME2.5" and conducted in vitro enzyme assays to determine the half-maximal inhibitory concentration values. We identified four hit compounds that inhibit T. cruzi SpdSyn (TcSpdSyn) by in silico and in vitro screening. We also determined the TcSpdSyn-hit compound complex structure using X-ray crystallography, which shows that the hit compound binds to the putrescine-binding site and interacts with Asp171 through a salt bridge.


  • Organizational Affiliation

    Advanced Computational Drug Discovery Unit, Institute of Innovative Research, Tokyo Institute of Technology, 4259-J3-23, Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Spermidine synthase, putative
A, B, C, D
304Trypanosoma cruzi strain CL BrenerMutation(s): 0 
Gene Names: Tc00.1047053510339.50
EC: 2.5.1.16
UniProt
Find proteins for Q4DA73 (Trypanosoma cruzi (strain CL Brener))
Explore Q4DA73 
Go to UniProtKB:  Q4DA73
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ4DA73
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
BSX Binding MOAD:  5B1S IC50: 1.24e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.58 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.188 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.484α = 87.91
b = 68.163β = 87.18
c = 94.458γ = 80.27
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
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: 2016-12-21
    Type: Initial release
  • Version 1.1: 2017-08-16
    Changes: Data collection, Database references
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Refinement description