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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==
<StructureSection load='1xt3' size='340' side='right' caption='[[1xt3]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
<StructureSection load='1xt3' size='340' side='right'caption='[[1xt3]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1XT3 FirstGlance]. <br>
<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>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
</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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xt3 OCA], [http://pdbe.org/1xt3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xt3 RCSB], [http://www.ebi.ac.uk/pdbsum/1xt3 PDBsum]</span></td></tr>
<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>
<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>
</table>
</table>
== Function ==
== Function ==
[[http://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>
[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>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xt/1xt3_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xt/1xt3_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
</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/chain_selection.php?pdb_ID=2ata ConSurf].
</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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==See Also==
==See Also==
*[[Cardiotoxin|Cardiotoxin]]
*[[Cardiotoxin 3D structures|Cardiotoxin 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Naja atra]]
[[Category: Naja atra]]
[[Category: Chen, C J]]
[[Category: Chen C-J]]
[[Category: Guan, H H]]
[[Category: Guan H-H]]
[[Category: Huang, W N]]
[[Category: Huang W-N]]
[[Category: Lee, S C]]
[[Category: Lee S-C]]
[[Category: Wang, C H]]
[[Category: Wang C-H]]
[[Category: Wu, W G]]
[[Category: Wu W-G]]
[[Category: Citrate]]
[[Category: Ctx-3]]
[[Category: Heparin]]
[[Category: Toxin]]

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