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| | ==Con-Vc11-22== | | ==Con-Vc11-22== |
| - | <StructureSection load='5kkm' size='340' side='right' caption='[[5kkm]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='5kkm' size='340' side='right'caption='[[5kkm]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kkm]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KKM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kkm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_victoriae Conus victoriae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KKM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KKM FirstGlance]. <br> |
| - | </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=5kkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kkm OCA], [http://pdbe.org/5kkm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kkm RCSB], [http://www.ebi.ac.uk/pdbsum/5kkm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kkm ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=5kkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kkm OCA], [https://pdbe.org/5kkm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kkm RCSB], [https://www.ebi.ac.uk/pdbsum/5kkm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kkm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/O2VC1_CONVC O2VC1_CONVC] Unknown. Intracranial injection of the peptide into mice does not produce toxic effects (PubMed:26774129). In addition, the peptide does not produce any observable changes to normal or depolarization-induced intracellular calcium levels in mouse dorsal root ganglion cells (PubMed:26774129).<ref>PMID:26774129</ref> |
| | <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: Chittoor, B]] | + | [[Category: Conus victoriae]] |
| - | [[Category: Krishnarjuna, B]] | + | [[Category: Large Structures]] |
| - | [[Category: MacRaild, C A]] | + | [[Category: Chittoor B]] |
| - | [[Category: Robinson, S D]] | + | [[Category: Krishnarjuna B]] |
| - | [[Category: Contryphan-vc1]] | + | [[Category: MacRaild CA]] |
| - | [[Category: Peptide scaffold]] | + | [[Category: Robinson SD]] |
| - | [[Category: Single disulfide-directed beta hairpin]]
| + | |
| - | [[Category: Stability]]
| + | |
| - | [[Category: Unknown function]]
| + | |
| Structural highlights
Function
O2VC1_CONVC Unknown. Intracranial injection of the peptide into mice does not produce toxic effects (PubMed:26774129). In addition, the peptide does not produce any observable changes to normal or depolarization-induced intracellular calcium levels in mouse dorsal root ganglion cells (PubMed:26774129).[1]
Publication Abstract from PubMed
Grafting bioactive peptide sequences onto small cysteine-rich scaffolds is a promising strategy for enhancing their stability and value as novel peptide-based therapeutics. However, correctly folded disulfide-rich peptides can be challenging to produce by either recombinant or synthetic means. The single disulfide-directed beta-hairpin (SDH) fold, first observed in contryphan-Vc1, provides a potential alternative to complex disulfide-rich scaffolds. We have undertaken recombinant production of full-length contryphan-Vc1 (rCon-Vc1[Z1Q]) and a truncated analogue (rCon-Vc11-22[Z1Q]), analyzed the backbone dynamics of rCon-Vc1[Z1Q], and probed the conformational and proteolytic stability of these peptides to evaluate the potential of contryphan-Vc1 as a molecular scaffold. Backbone 15N relaxation measurements for rCon-Vc1[Z1Q] indicate that the N-terminal domain of the peptide is ordered up to Thr19, whereas the remainder of the C-terminal region is highly flexible. The solution structure of truncated rCon-Vc11-22[Z1Q] was similar to that of the full-length peptide, indicating that the flexible C-terminus does not have any effect on the structured domain of the peptide. Contryphan-Vc1 exhibited excellent proteolytic stability against trypsin and chymotrypsin but was susceptible to pepsin digestion. We have investigated whether contryphan-Vc1 can accept a bioactive epitope while maintaining the structure of the peptide by introducing peptide sequences based on the DINNN motif of inducible nitric oxide synthase. We show that sCon-Vc11-22[NNN12-14] binds to the iNOS-binding protein SPSB2 with an affinity of 1.3 muM while maintaining the SDH fold. This study serves as a starting point in utilizing the SDH fold as a peptide scaffold.
The Single Disulfide-Directed beta-Hairpin Fold. Dynamics, Stability, and Engineering.,Chittoor B, Krishnarjuna B, Morales RAV, MacRaild CA, Sadek M, Leung EWW, Robinson SD, Pennington MW, Norton RS Biochemistry. 2017 May 16;56(19):2455-2466. doi: 10.1021/acs.biochem.7b00120., Epub 2017 May 2. PMID:28437072[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Robinson SD, Chhabra S, Belgi A, Chittoor B, Safavi-Hemami H, Robinson AJ, Papenfuss AT, Purcell AW, Norton RS. A Naturally Occurring Peptide with an Elementary Single Disulfide-Directed beta-Hairpin Fold. Structure. 2016 Jan 2. pii: S0969-2126(15)00504-3. doi:, 10.1016/j.str.2015.11.015. PMID:26774129 doi:http://dx.doi.org/10.1016/j.str.2015.11.015
- ↑ Chittoor B, Krishnarjuna B, Morales RAV, MacRaild CA, Sadek M, Leung EWW, Robinson SD, Pennington MW, Norton RS. The Single Disulfide-Directed beta-Hairpin Fold. Dynamics, Stability, and Engineering. Biochemistry. 2017 May 16;56(19):2455-2466. doi: 10.1021/acs.biochem.7b00120., Epub 2017 May 2. PMID:28437072 doi:http://dx.doi.org/10.1021/acs.biochem.7b00120
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