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== | ==Crystal Structure of Cardiotoxin VI from Taiwan Cobra (Naja atra) Venom== | ||
<StructureSection load='1ug4' size='340' side='right'caption='[[1ug4]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1ug4]] is a 1 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=1UG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UG4 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</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=1ug4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ug4 OCA], [https://pdbe.org/1ug4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ug4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ug4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ug4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/3SAN_NAJAT 3SAN_NAJAT] Basic protein that bind to cell membrane and depolarizes cardiomyocytes. This cytotoxin also shows lytic activities, on many other cells including red blood cells. Interaction with sulfatides in the cell membrane induces pore formation and cell internalization and is responsible for cytotoxicity in cardiomyocytes. It targets the mitochondrial membrane and induces mitochondrial swelling and fragmentation. Inhibits protein kinases C (By similarity). It binds to the integrin alpha-V/beta-3 with a moderate affinity (PubMed:16407244).<ref>PMID:16407244</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ug/1ug4_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</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/main_output.php?pdb_ID=1ug4 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Natural homologues of cobra cardiotoxins (CTXs) were classified into two structural subclasses of group I and II based on the amino acid sequence and circular dichroism analysis, but the exact differences in their three-dimensional structures and biological significance remain elusive. We show by circular dichroism, NMR spectroscopic, and X-ray crystallographic analyses of a newly purified group I CTX A6 from eastern Taiwan cobra (Naja atra) venoms that its loop I conformation adopts a type VIa turn with a cis peptide bond located between two proline residues of PPxY. A similar "banana-twisted" conformation can be observed in other group I CTXs and also in cyclolinopeptide A and its analogues. By binding to the membrane environment, group I CTX undergoes a conformational change to adopt a more extended hydrophobic domain with beta-sheet twisting closer to the one adopted by group II CTX. This result resolves a discrepancy in the CTX structural difference reported previously between solution as well as crystal state and shows that, in addition to the hydrophobicity, the exact loop I conformation also plays an important role in CTX-membrane interaction. Potential protein targets of group I CTXs after cell internalization are also discussed on the basis of the determined loop I conformation. | Natural homologues of cobra cardiotoxins (CTXs) were classified into two structural subclasses of group I and II based on the amino acid sequence and circular dichroism analysis, but the exact differences in their three-dimensional structures and biological significance remain elusive. We show by circular dichroism, NMR spectroscopic, and X-ray crystallographic analyses of a newly purified group I CTX A6 from eastern Taiwan cobra (Naja atra) venoms that its loop I conformation adopts a type VIa turn with a cis peptide bond located between two proline residues of PPxY. A similar "banana-twisted" conformation can be observed in other group I CTXs and also in cyclolinopeptide A and its analogues. By binding to the membrane environment, group I CTX undergoes a conformational change to adopt a more extended hydrophobic domain with beta-sheet twisting closer to the one adopted by group II CTX. This result resolves a discrepancy in the CTX structural difference reported previously between solution as well as crystal state and shows that, in addition to the hydrophobicity, the exact loop I conformation also plays an important role in CTX-membrane interaction. Potential protein targets of group I CTXs after cell internalization are also discussed on the basis of the determined loop I conformation. | ||
Structural difference between group I and group II cobra cardiotoxins: X-ray, NMR, and CD analysis of the effect of cis-proline conformation on three-fingered toxins.,Chen TS, Chung FY, Tjong SC, Goh KS, Huang WN, Chien KY, Wu PL, Lin HC, Chen CJ, Wu WG Biochemistry. 2005 May 24;44(20):7414-26. PMID:15895985<ref>PMID:15895985</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1ug4" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cardiotoxin 3D structures|Cardiotoxin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Naja atra]] | [[Category: Naja atra]] | ||
[[Category: Chen C-J]] | |||
[[Category: Chen | [[Category: Chung F-Y]] | ||
[[Category: Chung | [[Category: Wu W-G]] | ||
[[Category: Wu | |||