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| | ==NMR spatial structure of Tk-hefu peptide== | | ==NMR spatial structure of Tk-hefu peptide== |
| - | <StructureSection load='5lm0' size='340' side='right'caption='[[5lm0]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='5lm0' size='340' side='right'caption='[[5lm0]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lm0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aegilops_tauschii_x_triticum_timopheevii Aegilops tauschii x triticum timopheevii]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LM0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lm0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Triticum_kiharae Triticum kiharae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LM0 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">l-2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=376535 Aegilops tauschii x Triticum timopheevii])</td></tr> | + | </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=5lm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lm0 OCA], [https://pdbe.org/5lm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lm0 RCSB], [https://www.ebi.ac.uk/pdbsum/5lm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lm0 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=5lm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lm0 OCA], [http://pdbe.org/5lm0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lm0 RCSB], [http://www.ebi.ac.uk/pdbsum/5lm0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lm0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/R4ZAN8_TRIKH R4ZAN8_TRIKH] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aegilops tauschii x triticum timopheevii]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arseniev, A S]] | + | [[Category: Triticum kiharae]] |
| - | [[Category: Berkut, A A]] | + | [[Category: Arseniev AS]] |
| - | [[Category: Grishin, E V]] | + | [[Category: Berkut AA]] |
| - | [[Category: Mineev, K S]] | + | [[Category: Grishin EV]] |
| - | [[Category: Novikova, E V]] | + | [[Category: Mineev KS]] |
| - | [[Category: Oparin, P B]] | + | [[Category: Novikova EV]] |
| - | [[Category: Vassilevski, A A]] | + | [[Category: Oparin PB]] |
| - | [[Category: Anti microbial protein]]
| + | [[Category: Vassilevski AA]] |
| - | [[Category: Antimicrobial protein]]
| + | |
| - | [[Category: Protein]]
| + | |
| - | [[Category: Protein mutant plant defense peptide]]
| + | |
| Structural highlights
Function
R4ZAN8_TRIKH
Publication Abstract from PubMed
Tk-hefu is an artificial peptide designed based on the a-hairpinin scaffold, which selectively blocks voltage-gated potassium channels Kv1.3. Here we present its spatial structure resolved by NMR spectroscopy and analyze its interaction with channels using computer modeling. We apply Protein Surface Topography to suggest mutations and increase Tk-hefu affinity to Kv1.3 channel isoform. We redesign the functional surface of Tk-hefu to better match the respective surface of the channel pore vestibule. The resulting peptide Tk-hefu-2 retains Kv1.3 selectivity and displays ~20 times greater activity compared to Tk-hefu. We verify the mode of Tk-hefu-2 binding to the channel outer vestibule experimentally by site-directed mutagenesis. We argue that scaffold engineering aided by Protein Surface Topography represents a reliable tool for design and optimization of specific ion channel ligands.
Protein Surface Topography as a tool to enhance the selective activity of a potassium channel blocker.,Berkut AA, Chugunov AO, Mineev KS, Peigneur S, Tabakmakher VM, Krylov NA, Oparin PB, Lihonosova AF, Novikova EV, Arseniev AS, Grishin EV, Tytgat J, Efremov RG, Vassilevski AA J Biol Chem. 2019 Sep 18. pii: RA119.010494. doi: 10.1074/jbc.RA119.010494. PMID:31533989[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Berkut AA, Chugunov AO, Mineev KS, Peigneur S, Tabakmakher VM, Krylov NA, Oparin PB, Lihonosova AF, Novikova EV, Arseniev AS, Grishin EV, Tytgat J, Efremov RG, Vassilevski AA. Protein Surface Topography as a tool to enhance the selective activity of a potassium channel blocker. J Biol Chem. 2019 Sep 18. pii: RA119.010494. doi: 10.1074/jbc.RA119.010494. PMID:31533989 doi:http://dx.doi.org/10.1074/jbc.RA119.010494
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