View source for 2ldf


==Solution structure of the long sarafotoxin srtx-m==
<StructureSection load='2ldf' size='340' side='right'caption='[[2ldf]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ldf]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LDF FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2lde|2lde]]</div></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=2ldf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ldf OCA], [https://pdbe.org/2ldf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ldf RCSB], [https://www.ebi.ac.uk/pdbsum/2ldf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ldf ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/SRTXL_ATRMM SRTXL_ATRMM]] Vasoconstrictor activity. These toxins cause cardiac arrest probably as a result of coronary vasospasm. The major effects of sarafotoxin-m are a progressive decrease in heart rate (bradycardia) that turns into an arrhythmic phase that is followed by an A-V block.<ref>PMID:15350691</ref>   Sarafotoxin-m: vasoconstrictor activity. Causes cardiac arrest probably as a result of coronary vasospasm (By similarity). Displays low agonistic activities towards endothelin-2 receptor (EDNRB) (displays affinity in the micromolar range) (PubMed:21889567).<ref>PMID:15350691</ref> <ref>PMID:21889567</ref>  
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== Publication Abstract from PubMed ==
Long-sarafotoxins (l-SRTXs) have recently been identified in both the venom of Atractaspis microlepidota and that of Atractaspis irregularis. They are characterized by different C-terminus extensions that follow the invariant Trp21, which plays a crucial role in endothelin-receptor binding. We initially determined the toxicity and three-dimensional structures of two chemically synthesized l-SRTXs that have different C-terminus extensions, namely SRTX-m (24 aa, including extension "D-E-P") and SRTX-i3 (25 aa, including extension "V-N-R-N"). Both peptides were shown to be highly toxic in mice and displayed the cysteine-stabilized alpha-helical motif that characterizes endothelins and short-SRTXs, to which a longer C-terminus with variable flexibility is added. To discern the functional and pharmacological consequences of the supplementary amino acids, different chimerical as well as truncated forms of SRTX were designed and synthesized. Thus, we either removed the extra-C-terminal residues of SRTX-m or i3, or grafted the latter onto the C-terminal extremity of a short-SRTX (s-SRTX) (ie. SRTX-b). Our competitive binding assays where SRTXs competed for iodinated endothelin-1 binding to cloned ET(A) and ET(B) receptor subtypes over-expressed in CHO cells, revealed the essential role of the C-terminus extensions for ET-receptor recognition. Indeed, l-SRTXs displayed an affinity three to four orders of magnitude lower as compared to SRTX-b for the two receptor subtypes. Moreover, grafting the C-terminus extension to SRTX-b induced a drastic decrease in affinity, while its removal (truncated l-SRTXs) yielded an affinity for ET-receptors similar to that of s-SRTXs. Furthermore, we established by intracellular Ca(2+) measurements that l-SRTXs, as well as s-SRTXs, display agonistic activities. We thus confirmed in these functional assays the major difference in potency for these two SRTX families as well as the crucial role of the C-terminus extension in their various pharmacological profiles. Finally, one of the chimeric toxin synthesized in this study appears to be one of the most potent and selective ligand of the ET(B) receptor known to date.

Pharmacological and structural characterization of long-sarafotoxins, a new family of endothelin-like peptides: Role of the C-terminus extension.,Mourier G, Hajj M, Cordier F, Zorba A, Gao X, Coskun T, Herbet A, Marcon E, Beau F, Delepierre M, Ducancel F, Servent D Biochimie. 2011 Aug 29. PMID:21889567<ref>PMID:21889567</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2ldf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Cordier, F]]
[[Category: Delepierre, M]]
[[Category: Ducancel, F]]
[[Category: Hajj, M]]
[[Category: Servent, D]]
[[Category: Zorba, A]]
[[Category: Endothelin-like peptide]]
[[Category: Toxin]]