4L5C

Methylthioadenosine phosphorylase from Schistosoma mansoni in complex with adenine in space group P212121


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.08 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.193 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Crystal Structure of Schistosoma mansoni Adenosine Phosphorylase/5'-Methylthioadenosine Phosphorylase and Its Importance on Adenosine Salvage Pathway.

Torini, J.R.Brandao-Neto, J.DeMarco, R.Pereira, H.D.

(2016) PLoS Negl Trop Dis 10: e0005178-e0005178

  • DOI: https://doi.org/10.1371/journal.pntd.0005178
  • Primary Citation of Related Structures:  
    4L5A, 4L5C, 4L5Y, 4L6I, 5F73, 5F76, 5F77, 5F78, 5F7J, 5F7O, 5F7X, 5F7Z, 5FAK

  • PubMed Abstract: 

    Schistosoma mansoni do not have de novo purine pathways and rely on purine salvage for their purine supply. It has been demonstrated that, unlike humans, the S. mansoni is able to produce adenine directly from adenosine, although the enzyme responsible for this activity was unknown. In the present work we show that S. mansoni 5´-deoxy-5´-methylthioadenosine phosphorylase (MTAP, E.C. 2.4.2.28) is capable of use adenosine as a substrate to the production of adenine. Through kinetics assays, we show that the Schistosoma mansoni MTAP (SmMTAP), unlike the mammalian MTAP, uses adenosine substrate with the same efficiency as MTA phosphorolysis, which suggests that this enzyme is part of the purine pathway salvage in S. mansoni and could be a promising target for anti-schistosoma therapies. Here, we present 13 SmMTAP structures from the wild type (WT), including three single and one double mutant, and generate a solid structural framework for structure description. These crystal structures of SmMTAP reveal that the active site contains three substitutions within and near the active site when compared to it mammalian counterpart, thus opening up the possibility of developing specific inhibitors to the parasite MTAP. The structural and kinetic data for 5 substrates reveal the structural basis for this interaction, providing substract for inteligent design of new compounds for block this enzyme activity.


  • Organizational Affiliation

    Laboratório de Biologia Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
S-methyl-5'-thioadenosine phosphorylase
A, B, C, D, E
A, B, C, D, E, F
320Schistosoma mansoniMutation(s): 0 
Gene Names: SmMTAP
EC: 2.4.2.28
UniProt
Find proteins for I0B503 (Schistosoma mansoni)
Explore I0B503 
Go to UniProtKB:  I0B503
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupI0B503
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ADE
Query on ADE

Download Ideal Coordinates CCD File 
G [auth A]
I [auth B]
K [auth C]
M [auth D]
P [auth E]
G [auth A],
I [auth B],
K [auth C],
M [auth D],
P [auth E],
R [auth F]
ADENINE
C5 H5 N5
GFFGJBXGBJISGV-UHFFFAOYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
H [auth A]
J [auth B]
L [auth C]
N [auth D]
O [auth D]
H [auth A],
J [auth B],
L [auth C],
N [auth D],
O [auth D],
Q [auth E]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.08 Å
  • R-Value Free: 0.222 
  • R-Value Work: 0.191 
  • R-Value Observed: 0.193 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 102.58α = 90
b = 135.71β = 90
c = 145.05γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
GDAdata collection
xia2data reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-06-11
    Type: Initial release
  • Version 1.1: 2016-12-21
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description