6CE2

Crystal structure of Myotoxin I (MjTX-I) from Bothrops moojeni complexed to inhibitor suramin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.222 

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This is version 1.3 of the entry. See complete history


Literature

Structural and functional characterization of suramin-bound MjTX-I from Bothrops moojeni suggests a particular myotoxic mechanism.

Salvador, G.H.M.Dreyer, T.R.Gomes, A.A.S.Cavalcante, W.L.G.Dos Santos, J.I.Gandin, C.A.de Oliveira Neto, M.Gallacci, M.Fontes, M.R.M.

(2018) Sci Rep 8: 10317-10317

  • DOI: https://doi.org/10.1038/s41598-018-28584-7
  • Primary Citation of Related Structures:  
    6CE2

  • PubMed Abstract: 

    Local myonecrosis is the main event resulting from snakebite envenomation by the Bothrops genus and, frequently, it is not efficiently neutralized by antivenom administration. Proteases, phospholipases A 2 (PLA 2 ) and PLA 2 -like toxins are found in venom related to muscle damage. Functional sites responsible for PLA 2 -like toxins activity have been proposed recently; they consist of a membrane docking-site and a membrane rupture-site. Herein, a combination of functional, biophysical and crystallographic techniques was used to characterize the interaction between suramin and MjTX-I (a PLA 2 -like toxin from Bothrops moojeni venom). Functional in vitro neuromuscular assays were performed to study the biological effects of the protein-ligand interaction, demonstrating that suramin neutralizes the myotoxic effect of MjTX-I. Calorimetric assays showed two different binding events: (i) inhibitor-protein interactions and (ii) toxin oligomerization processes. These hypotheses were also corroborated with dynamic light and small angle X-ray scattering assays. The crystal structure of the MjTX-I/suramin showed a totally different interaction mode compared to other PLA 2 -like/suramin complexes. Thus, we suggested a novel myotoxic mechanism for MjTX-I that may be inhibited by suramin. These results can further contribute to the search for inhibitors that will efficiently counteract local myonecrosis in order to be used as an adjuvant of conventional serum therapy.


  • Organizational Affiliation

    Universidade Estadual Paulista (UNESP), Instituto de Biociências, Dep. de Física e Biofísica, Botucatu, SP, Brazil.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Basic phospholipase A2 homolog 1
A, B
121Bothrops moojeniMutation(s): 0 
UniProt
Find proteins for P82114 (Bothrops moojeni)
Explore P82114 
Go to UniProtKB:  P82114
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP82114
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SVR (Subject of Investigation/LOI)
Query on SVR

Download Ideal Coordinates CCD File 
E [auth B]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 
C [auth A],
D [auth B]
2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL
C16 H34 O8
PJWQOENWHPEPKI-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SVR Binding MOAD:  6CE2 Kd: 500 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.15 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.222 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.748α = 90
b = 60.283β = 90
c = 102.275γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
DENZOdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Sao Paulo Research Foundation (FAPESP)Brazil2015/24167-7

Revision History  (Full details and data files)

  • Version 1.0: 2018-07-25
    Type: Initial release
  • Version 1.1: 2019-04-17
    Changes: Author supporting evidence, Data collection
  • Version 1.2: 2020-01-01
    Changes: Author supporting evidence
  • Version 1.3: 2023-10-04
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary