4YV5

Crystal Structure of Myotoxin II from Bothrops moojeni complexed to Suramin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.196 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural and functional evidence for membrane docking and disruption sites on phospholipase A2-like proteins revealed by complexation with the inhibitor suramin.

Salvador, G.H.Dreyer, T.R.Cavalcante, W.L.Matioli, F.F.Dos Santos, J.I.Velazquez-Campoy, A.Gallacci, M.Fontes, M.R.

(2015) Acta Crystallogr D Biol Crystallogr 71: 2066-2078

  • DOI: https://doi.org/10.1107/S1399004715014443
  • Primary Citation of Related Structures:  
    4YV5

  • PubMed Abstract: 

    Local myonecrosis resulting from snakebite envenomation is not efficiently neutralized by regular antivenom administration. This limitation is considered to be a significant health problem by the World Health Organization. Phospholipase A2-like (PLA2-like) proteins are among the most important proteins related to the muscle damage resulting from several snake venoms. However, despite their conserved tertiary structure compared with PLA2s, their biological mechanism remains incompletely understood. Different oligomeric conformations and binding sites have been identified or proposed, leading to contradictory data in the literature. In the last few years, a comprehensive hypothesis has been proposed based on fatty-acid binding, allosteric changes and the presence of two different interaction sites. In the present study, a combination of techniques were used to fully understand the structural-functional characteristics of the interaction between suramin and MjTX-II (a PLA2-like toxin). In vitro neuromuscular studies were performed to characterize the biological effects of the protein-ligand interaction and demonstrated that suramin neutralizes the myotoxic activity of MjTX-II. The high-resolution structure of the complex identified the toxin-ligand interaction sites. Calorimetric assays showed two different binding events between the protein and the inhibitor. It is demonstrated for the first time that the inhibitor binds to the surface of the toxin, obstructing the sites involved in membrane docking and disruption according to the proposed myotoxic mechanism. Furthermore, higher-order oligomeric formation by interaction with interfacial suramins was observed, which may also aid the inhibitory process. These results further substantiate the current myotoxic mechanism and shed light on the search for efficient inhibitors of the local myonecrosis phenomenon.


  • Organizational Affiliation

    Department of Physics and Biophysics, Institute of Biosciences, UNESP - Universidade Estadual Paulista, Botucatu-SP, Brazil.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Basic phospholipase A2 homolog 2A [auth B],
B [auth A]
122Bothrops moojeniMutation(s): 0 
UniProt
Find proteins for Q9I834 (Bothrops moojeni)
Explore Q9I834 
Go to UniProtKB:  Q9I834
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9I834
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SVR
Query on SVR

Download Ideal Coordinates CCD File 
I [auth B],
N [auth A]
8,8'-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFON IC ACID
C51 H40 N6 O23 S6
FIAFUQMPZJWCLV-UHFFFAOYSA-N
PE4
Query on PE4

Download Ideal Coordinates CCD File 
E [auth B]2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL
C16 H34 O8
PJWQOENWHPEPKI-UHFFFAOYSA-N
1PE
Query on 1PE

Download Ideal Coordinates CCD File 
F [auth B],
L [auth A]
PENTAETHYLENE GLYCOL
C10 H22 O6
JLFNLZLINWHATN-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
C [auth B]
D [auth B]
G [auth B]
H [auth B]
J [auth A]
C [auth B],
D [auth B],
G [auth B],
H [auth B],
J [auth A],
K [auth A],
M [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
SVR Binding MOAD:  4YV5 Kd: 600 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.196 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.795α = 90
b = 63.646β = 90
c = 87.721γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data scaling
SCALEPACKdata scaling
PHASERphasing
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-10-14
    Type: Initial release
  • Version 1.1: 2017-11-22
    Changes: Derived calculations, Refinement description
  • Version 1.2: 2018-04-18
    Changes: Data collection, Database references
  • Version 1.3: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary