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2j15

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Revision as of 14:48, 17 November 2021

Cyclic MrIA: An exceptionally stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter.

Structural highlights

2j15 is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CT1A_CONMR] Chi-conotoxins inhibit the neuronal noradrenaline transporter (NET/SLC6A2).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Conotoxins, disulfide-rich peptides from the venom of cone snails, have created much excitement over recent years due to their potency and specificity for ion channels and their therapeutic potential. One recently identified conotoxin, MrIA, a 13-residue member of the chi-conotoxin family, inhibits the human norepinephrine transporter (NET) and has potential applications in the treatment of pain. In the current study, we show that the beta-hairpin structure of native MrIA is retained in a synthetic cyclic version, as is biological activity at the NET. Furthermore, the cyclic version has increased resistance to trypsin digestion relative to the native peptide, an intriguing result because the cleavage site for the trypsin is not close to the cyclization site. The use of peptides as drugs is generally hampered by susceptibility to proteolysis, and so, the increase in enzymatic stability against trypsin observed in the current study may be useful in improving the therapeutic potential of MrIA. Furthermore, the structure reported here for cyclic MrIA represents a new topology among a growing number of circular disulfide-rich peptides.

Cyclic MrIA: a stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter.,Lovelace ES, Armishaw CJ, Colgrave ML, Wahlstrom ME, Alewood PF, Daly NL, Craik DJ J Med Chem. 2006 Nov 2;49(22):6561-8. PMID:17064074^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sharpe IA, Gehrmann J, Loughnan ML, Thomas L, Adams DA, Atkins A, Palant E, Craik DJ, Adams DJ, Alewood PF, Lewis RJ. Two new classes of conopeptides inhibit the alpha1-adrenoceptor and noradrenaline transporter. Nat Neurosci. 2001 Sep;4(9):902-7. PMID:11528421 doi:http://dx.doi.org/10.1038/nn0901-902
↑ Bryan-Lluka LJ, Bonisch H, Lewis RJ. chi-Conopeptide MrIA partially overlaps desipramine and cocaine binding sites on the human norepinephrine transporter. J Biol Chem. 2003 Oct 10;278(41):40324-9. Epub 2003 Jul 1. PMID:12837768 doi:http://dx.doi.org/10.1074/jbc.M213101200
↑ Sharpe IA, Palant E, Schroeder CI, Kaye DM, Adams DJ, Alewood PF, Lewis RJ. Inhibition of the norepinephrine transporter by the venom peptide chi-MrIA. Site of action, Na+ dependence, and structure-activity relationship. J Biol Chem. 2003 Oct 10;278(41):40317-23. Epub 2003 Jul 28. PMID:12885787 doi:http://dx.doi.org/10.1074/jbc.M213030200
↑ Nielsen CK, Lewis RJ, Alewood D, Drinkwater R, Palant E, Patterson M, Yaksh TL, McCumber D, Smith MT. Anti-allodynic efficacy of the chi-conopeptide, Xen2174, in rats with neuropathic pain. Pain. 2005 Nov;118(1-2):112-24. Epub 2005 Sep 9. PMID:16154696 doi:http://dx.doi.org/S0304-3959(05)00384-2
↑ Lovelace ES, Armishaw CJ, Colgrave ML, Wahlstrom ME, Alewood PF, Daly NL, Craik DJ. Cyclic MrIA: a stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter. J Med Chem. 2006 Nov 2;49(22):6561-8. PMID:17064074 doi:http://dx.doi.org/10.1021/jm060299h

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2j15"

@@ Line 3: / Line 3: @@
 <StructureSection load='2j15' size='340' side='right'caption='[[2j15]], [[NMR_Ensembles_of_Models | 21 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2j15]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J15 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J15 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2j15]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J15 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J15 FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</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=2j15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j15 OCA], [http://pdbe.org/2j15 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j15 RCSB], [http://www.ebi.ac.uk/pdbsum/2j15 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j15 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=2j15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j15 OCA], [https://pdbe.org/2j15 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j15 RCSB], [https://www.ebi.ac.uk/pdbsum/2j15 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j15 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CT1A_CONMR CT1A_CONMR]] Chi-conotoxins inhibit the neuronal noradrenaline transporter (NET/SLC6A2).<ref>PMID:11528421</ref> <ref>PMID:12837768</ref> <ref>PMID:12885787</ref> <ref>PMID:16154696</ref>
+[[https://www.uniprot.org/uniprot/CT1A_CONMR CT1A_CONMR]] Chi-conotoxins inhibit the neuronal noradrenaline transporter (NET/SLC6A2).<ref>PMID:11528421</ref> <ref>PMID:12837768</ref> <ref>PMID:12885787</ref> <ref>PMID:16154696</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

2j15

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Revision as of 14:48, 17 November 2021

Cyclic MrIA: An exceptionally stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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