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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'''
| | ===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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_15590643}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 15590643 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_15590643}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Ctx-3]] | | [[Category: Ctx-3]] |
| [[Category: Heparin]] | | [[Category: Heparin]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:28:38 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 19:43:21 2008'' |
