1xt3

Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3

Structural highlights 1xt3 is a 2 chain structure with sequence from Naja atra. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cardiotoxin

spinqualitylabelsall models 1xt3, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image