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==Exploring Cystine Dense Peptide Space to Open a Unique Molecular Toolbox==
==Exploring Cystine Dense Peptide Space to Open a Unique Molecular Toolbox==
<StructureSection load='6aup' size='340' side='right' caption='[[6aup]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
<StructureSection load='6aup' size='340' side='right'caption='[[6aup]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6aup]] is a 16 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AUP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AUP FirstGlance]. <br>
<table><tr><td colspan='2'>[[6aup]] is a 16 chain structure with sequence from [https://en.wikipedia.org/wiki/Mesobuthus_martensii Mesobuthus martensii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AUP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AUP FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.95&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6au7|6au7]], [[6atl|6atl]], [[6atn|6atn]], [[6ats|6ats]], [[6atu|6atu]], [[6atw|6atw]], [[6aty|6aty]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6aup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aup OCA], [http://pdbe.org/6aup PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aup RCSB], [http://www.ebi.ac.uk/pdbsum/6aup PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aup ProSAT]</span></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=6aup FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aup OCA], [https://pdbe.org/6aup PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aup RCSB], [https://www.ebi.ac.uk/pdbsum/6aup PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aup ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/KGX22_MESMA KGX22_MESMA]] Blocks human and/or rat Kv11.1/KCNH2/ERG1, Kv11.2/KCNH6/ERG2 and Kv11.3/KCNH7/ERG3 by binding to channel outer vestibule (S5P domain) with a 1:1 stoichiometry. Has also a minimal effect on rat ELK1/KCNH4 potassium channels.[UniProtKB:Q9BKB7]  
[https://www.uniprot.org/uniprot/KGX22_MESMA KGX22_MESMA] Blocks human and/or rat Kv11.1/KCNH2/ERG1, Kv11.2/KCNH6/ERG2 and Kv11.3/KCNH7/ERG3 by binding to channel outer vestibule (S5P domain) with a 1:1 stoichiometry. Has also a minimal effect on rat ELK1/KCNH4 potassium channels.[UniProtKB:Q9BKB7]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Peptides folded through interwoven disulfides display extreme biochemical properties and unique medicinal potential. However, their exploitation has been hampered by the limited amounts isolatable from natural sources and the expense of chemical synthesis. We developed reliable biological methods for high-throughput expression, screening and large-scale production of these peptides: 46 were successfully produced in multimilligram quantities, and &gt;600 more were deemed expressible through stringent screening criteria. Many showed extreme resistance to temperature, proteolysis and/or reduction, and all displayed inhibitory activity against at least 1 of 20 ion channels tested, thus confirming their biological functionality. Crystal structures of 12 confirmed proper cystine topology and the utility of crystallography to study these molecules but also highlighted the need for rational classification. Previous categorization attempts have focused on limited subsets featuring distinct motifs. Here we present a global definition, classification and analysis of &gt;700 structures of cystine-dense peptides, providing a unifying framework for these molecules.
 
Screening, large-scale production and structure-based classification of cystine-dense peptides.,Correnti CE, Gewe MM, Mehlin C, Bandaranayake AD, Johnsen WA, Rupert PB, Brusniak MY, Clarke M, Burke SE, De Van Der Schueren W, Pilat K, Turnbaugh SM, May D, Watson A, Chan MK, Bahl CD, Olson JM, Strong RK Nat Struct Mol Biol. 2018 Mar;25(3):270-278. doi: 10.1038/s41594-018-0033-9. Epub, 2018 Feb 26. PMID:29483648<ref>PMID:29483648</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6aup" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Gewe, M M]]
[[Category: Large Structures]]
[[Category: Rupert, P]]
[[Category: Mesobuthus martensii]]
[[Category: Strong, R K]]
[[Category: Gewe MM]]
[[Category: Cystine knot]]
[[Category: Rupert P]]
[[Category: Knottin]]
[[Category: Strong RK]]
[[Category: Toxin]]

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