1xt3

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{{STRUCTURE_1xt3| PDB=1xt3 | SCENE= }}
{{STRUCTURE_1xt3| PDB=1xt3 | SCENE= }}
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'''Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3'''
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===Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 15590643 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15590643}}
==About this Structure==
==About this Structure==
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[[Category: Ctx-3]]
[[Category: Ctx-3]]
[[Category: Heparin]]
[[Category: Heparin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:28:38 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 19:43:21 2008''

Revision as of 16:43, 28 July 2008

Template:STRUCTURE 1xt3

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

Template:ABSTRACT PUBMED 15590643

About this Structure

1XT3 is a Single protein structure of sequence from Naja atra. Full crystallographic information is available from OCA.

Reference

Structural basis of citrate-dependent and heparan sulfate-mediated cell surface retention of cobra cardiotoxin A3., Lee SC, Guan HH, Wang CH, Huang WN, Tjong SC, Chen CJ, Wu WG, J Biol Chem. 2005 Mar 11;280(10):9567-77. Epub 2004 Dec 6. PMID:15590643

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