1jzp

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[[Image:1jzp.gif|left|200px]]
 
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==Modified Peptide A (D18-A1) of the Rabbit Skeletal Dihydropyridine Receptor==
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The line below this paragraph, containing "STRUCTURE_1jzp", creates the "Structure Box" on the page.
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<StructureSection load='1jzp' size='340' side='right'caption='[[1jzp]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1jzp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JZP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JZP FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 1 model</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
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{{STRUCTURE_1jzp| PDB=1jzp | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jzp OCA], [https://pdbe.org/1jzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jzp RCSB], [https://www.ebi.ac.uk/pdbsum/1jzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jzp ProSAT]</span></td></tr>
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</table>
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'''Modified Peptide A (D18-A1) of the Rabbit Skeletal Dihydropyridine Receptor'''
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== Function ==
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[https://www.uniprot.org/uniprot/CAC1S_RABIT CAC1S_RABIT] Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle.
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<div style="background-color:#fffaf0;">
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==Overview==
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== Publication Abstract from PubMed ==
An alpha-helical II-III loop segment of the dihydropyridine receptor activates the ryanodine receptor calcium-release channel. We describe a novel manipulation in which this agonist's activity is increased by modifying its surface structure to resemble that of a toxin molecule. In a unique system, native beta-sheet scorpion toxins have been reported to activate skeletal muscle ryanodine receptor calcium channels with high affinity by binding to the same site as the lower-affinity alpha-helical dihydropyridine receptor segment. We increased the alignment of basic residues in the alpha-helical peptide to mimic the spatial orientation of active residues in the scorpion toxin, with a consequent 2-20-fold increase in the activity of the alpha-helical peptide. We hypothesized that, like the native peptide, the modified peptide and the scorpion toxin may bind to a common site. This was supported by (i) similar changes in ryanodine receptor channel gating induced by the native or modified alpha-helical peptide and the beta-sheet toxin, a 10-100-fold reduction in channel closed time, with a &lt; or = 2-fold increase in open dwell time and (ii) a failure of the toxin to further activate channels activated by the peptides. These results suggest that diverse structural scaffolds can present similar conformational surface properties to target common receptor sites.
An alpha-helical II-III loop segment of the dihydropyridine receptor activates the ryanodine receptor calcium-release channel. We describe a novel manipulation in which this agonist's activity is increased by modifying its surface structure to resemble that of a toxin molecule. In a unique system, native beta-sheet scorpion toxins have been reported to activate skeletal muscle ryanodine receptor calcium channels with high affinity by binding to the same site as the lower-affinity alpha-helical dihydropyridine receptor segment. We increased the alignment of basic residues in the alpha-helical peptide to mimic the spatial orientation of active residues in the scorpion toxin, with a consequent 2-20-fold increase in the activity of the alpha-helical peptide. We hypothesized that, like the native peptide, the modified peptide and the scorpion toxin may bind to a common site. This was supported by (i) similar changes in ryanodine receptor channel gating induced by the native or modified alpha-helical peptide and the beta-sheet toxin, a 10-100-fold reduction in channel closed time, with a &lt; or = 2-fold increase in open dwell time and (ii) a failure of the toxin to further activate channels activated by the peptides. These results suggest that diverse structural scaffolds can present similar conformational surface properties to target common receptor sites.
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==About this Structure==
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The three-dimensional structural surface of two beta-sheet scorpion toxins mimics that of an alpha-helical dihydropyridine receptor segment.,Green D, Pace S, Curtis SM, Sakowska M, Lamb GD, Dulhunty AF, Casarotto MG Biochem J. 2003 Mar 1;370(Pt 2):517-27. PMID:12429019<ref>PMID:12429019</ref>
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Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JZP OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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The three-dimensional structural surface of two beta-sheet scorpion toxins mimics that of an alpha-helical dihydropyridine receptor segment., Green D, Pace S, Curtis SM, Sakowska M, Lamb GD, Dulhunty AF, Casarotto MG, Biochem J. 2003 Mar 1;370(Pt 2):517-27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12429019 12429019]
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</div>
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[[Category: Casarotto, M G.]]
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<div class="pdbe-citations 1jzp" style="background-color:#fffaf0;"></div>
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[[Category: Dulhunty, A F.]]
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== References ==
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[[Category: Green, D.]]
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<references/>
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[[Category: Pace, S.]]
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__TOC__
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[[Category: Sakowska, M.]]
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</StructureSection>
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[[Category: Alpha helical peptide]]
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[[Category: Large Structures]]
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[[Category: D-isomer]]
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[[Category: Oryctolagus cuniculus]]
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[[Category: Dhpr]]
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[[Category: Casarotto MG]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:07:06 2008''
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[[Category: Dulhunty AF]]
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[[Category: Green D]]
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[[Category: Pace S]]
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[[Category: Sakowska M]]

Current revision

Modified Peptide A (D18-A1) of the Rabbit Skeletal Dihydropyridine Receptor

PDB ID 1jzp

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