1xt3

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[[Image:1xt3.png|left|200px]]
 
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{{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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<StructureSection load='1xt3' size='340' side='right'caption='[[1xt3]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1xt3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_atra Naja atra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XT3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XT3 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xt3 OCA], [https://pdbe.org/1xt3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xt3 RCSB], [https://www.ebi.ac.uk/pdbsum/1xt3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xt3 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/3SA3_NAJAT 3SA3_NAJAT] Basic protein that binds to cell membrane and depolarizes cardiomyocytes. This cytotoxin also possesses lytic activity on many other cells, including red blood cells (PubMed:8182052). Interaction with sulfatides in the cell membrane induces pore formation and cell internalization. Cytotoxicity is due to pore formation, and to another mechanism independent of membrane-damaging activity. When internalized, it targets the mitochondrial membrane and induces mitochondrial swelling and fragmentation. It inhibits protein kinases C. It binds to the integrin alpha-V/beta-3 (ITGAV/ITGB3) with a moderate affinity (PubMed:16407244). It also binds with high affinity to heparin (PubMed:17685633).<ref>PMID:15922335</ref> <ref>PMID:16263708</ref> <ref>PMID:16407244</ref> <ref>PMID:17714752</ref> <ref>PMID:8182052</ref> <ref>PMID:8448165</ref> <ref>PMID:9245415</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xt/1xt3_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1xt3 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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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===Structure Basis of Venom Citrate-Dependent Heparin Sulfate-Mediated Cell Surface Retention of Cobra Cardiotoxin A3===
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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<ref>PMID:15590643</ref>
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{{ABSTRACT_PUBMED_15590643}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 1xt3" style="background-color:#fffaf0;"></div>
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[[1xt3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Naja_atra Naja atra]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XT3 OCA].
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==See Also==
==See Also==
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*[[Cardiotoxin|Cardiotoxin]]
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*[[Cardiotoxin 3D structures|Cardiotoxin 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:015590643</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Naja atra]]
[[Category: Naja atra]]
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[[Category: Chen, C J.]]
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[[Category: Chen C-J]]
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[[Category: Guan, H H.]]
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[[Category: Guan H-H]]
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[[Category: Huang, W N.]]
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[[Category: Huang W-N]]
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[[Category: Lee, S C.]]
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[[Category: Lee S-C]]
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[[Category: Wang, C H.]]
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[[Category: Wang C-H]]
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[[Category: Wu, W G.]]
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[[Category: Wu W-G]]
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[[Category: Citrate]]
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[[Category: Ctx-3]]
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[[Category: Heparin]]
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[[Category: Toxin]]
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Current revision

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

PDB ID 1xt3

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