5epm: Difference between revisions
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<StructureSection load='5epm' size='340' side='right' caption='[[5epm]], [[Resolution|resolution]] 1.75Å' scene=''> | <StructureSection load='5epm' size='340' side='right' caption='[[5epm]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5epm]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EPM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EPM FirstGlance]. <br> | <table><tr><td colspan='2'>[[5epm]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EPM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EPM FirstGlance]. <br> | ||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=5epm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5epm OCA], [http://pdbe.org/5epm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5epm RCSB], [http://www.ebi.ac.uk/pdbsum/5epm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5epm ProSAT]</span></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=5epm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5epm OCA], [http://pdbe.org/5epm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5epm RCSB], [http://www.ebi.ac.uk/pdbsum/5epm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5epm ProSAT]</span></td></tr> | ||
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</div> | </div> | ||
<div class="pdbe-citations 5epm" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5epm" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[3D structures of antibody|3D structures of antibody]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Lk3 transgenic mice]] | |||
[[Category: Rossi, A]] | [[Category: Rossi, A]] | ||
[[Category: Shcherbatko, A]] | [[Category: Shcherbatko, A]] | ||
Revision as of 12:55, 22 November 2017
Ceratotoxin variant in complex with specific antibody Fab fragmentCeratotoxin variant in complex with specific antibody Fab fragment
Structural highlights
Publication Abstract from PubMedThe prominent role of voltage-gated sodium channel 1.7 (Nav1.7) in nociception was revealed by remarkable human clinical and genetic evidence. Development of potent and subtypeselective inhibitors of this ion channel is crucial for obtaining therapeutically useful analgesic compounds. Microproteins isolated from animal venoms have been identified as promising therapeutic leads for ion channels, since they naturally evolved to be potent ion channel blockers. Here we report the engineering of highly potent and selective inhibitors of Nav1.7 channel based on tarantula Ceratotoxin-1 (CcoTx1). We utilized a combination of directed evolution, saturation mutagenesis, chemical modification, and rational drug design to obtain higher potency and selectivity to Nav1.7 channel. The resulting microproteins are highly potent (IC50 to Nav1.7 of 2.5 nM) and selective. We achieved 80-fold and 20-fold selectivity over the closely related Nav1.2 and Nav1.6 channels, respectively, and the IC50 on skeletal (Nav1.4) and cardiac (Nav1.5) sodium channels is above 3000nM. The lead molecules have the potential for future clinical development as novel therapeutics in the treatment of pain. Engineering Highly Potent and Selective Microproteins Against Nav1.7 Sodium Channel for Treatment of Pain.,Shcherbatko A, Rossi A, Foletti D, Zhu G, Bogin O, Galindo-Casas M, Rickert M, Hasa-Moreno A, Bartevitch V, Crameri A, Steiner AR, Henningsen R, Gill A, Pons J, Shelton DL, Rajpal A, Strop P J Biol Chem. 2016 Apr 22. pii: jbc.M116.725978. PMID:27129258[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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