1XT3

Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.227 
  • R-Value Observed: 0.231 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Structural basis of citrate-dependent and heparan sulfate-mediated cell surface retention of cobra cardiotoxin A3

Lee, S.-C.Guan, H.-H.Wang, C.-H.Huang, W.-N.Tjong, S.-C.Chen, C.-J.Wu, W.-G.

(2005) J Biol Chem 280: 9567-9577

  • DOI: https://doi.org/10.1074/jbc.M412398200
  • Primary Citation of Related Structures:  
    1XT3

  • PubMed Abstract: 

    Anionic citrate is a major component of venom, but the role of venom citrate in toxicity other than its inhibitory effect on the cation-dependent action of venom toxins is poorly understood. By immobilizing Chinese hamster ovary cells in microcapillary tubes and heparin on sensor chips, we demonstrated that heparan sulfate-mediated cell retention of the major cardiotoxin (CTX) from the Taiwan cobra, CTX A3, near membrane surfaces is citrate-dependent. X-ray determination of a CTX A3-heparin hexasaccharide complex structure at 2.4 A resolution revealed a molecular mechanism for toxin retention in which heparin-induced conformational changes of CTX A3 lead to citrate-mediated dimerization. A citrate ion bound to Lys-23 and Lys-31 near the tip of loop II stabilizes hydrophobic contact of the CTX A3 homodimer at the functionally important loop I and II regions. Additionally, the heparin hexasaccharide interacts with five CTX A3 molecules in the crystal structure, providing another mechanism whereby the toxin establishes a complex network of interactions that result in a strong interaction with cell surfaces presenting heparan sulfate. Our results suggest a novel role for venom citrate in biological activity and reveal a structural model that explains cell retention of cobra CTX A3 through heparan sulfate-CTX interactions.


  • Organizational Affiliation

    Institute of Bioinformatics and Structural Biology, National TsingHua University, Hsinchu 30043, Taiwan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cytotoxin 3
A, B
60Naja atraMutation(s): 0 
UniProt
Find proteins for P60301 (Naja atra)
Explore P60301 
Go to UniProtKB:  P60301
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP60301
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose
C
6N/A
Glycosylation Resources
GlyTouCan:  G30141AL
GlyCosmos:  G30141AL
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CIT
Query on CIT

Download Ideal Coordinates CCD File 
D [auth A]CITRIC ACID
C6 H8 O7
KRKNYBCHXYNGOX-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.227 
  • R-Value Observed: 0.231 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 43.903α = 90
b = 59.447β = 90
c = 98.62γ = 90
Software Package:
Software NamePurpose
XDSdata scaling
SCALEPACKdata scaling
CNSrefinement
XDSdata reduction
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-12-14
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary