2ew4

From Proteopedia

(Difference between revisions)

Current revision

Solution structure of MrIA

Structural highlights

2ew4 is a 1 chain structure with sequence from Conus marmoreus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CTA1A_CONMR Chi-conotoxins inhibit the neuronal noradrenaline transporter (NET/SLC6A2) (PubMed:11528421, PubMed:12837768, PubMed:12885787, PubMed:16154696). Activity has been described on both human (inhibition of norepinephrine uptake is IC(50)=1.26 uM) and rat (pIC(50)=6.21 corresponding IC(50)=0.16 uM) transporters (PubMed:11528421, PubMed:12885787). Acts as a reversible non-competitive inhibitor (PubMed:11528421).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The chi-conopeptides MrIA and MrIB are 13-residue peptides with two disulfide bonds that inhibit human and rat norepinephrine transporter systems and are of significant interest for the design of novel drugs involved in pain treatment. In the current study we have determined the solution structure of MrIA using NMR spectroscopy. The major element of secondary structure is a beta-hairpin with the two strands connected by an inverse gamma-turn. The residues primarily involved in activity have previously been shown to be located in the turn region (Sharpe, I. A.; Palant, E.; Schroder, C. I.; Kaye, D. M.; Adams, D. J.; Alewood, P. F.; Lewis, R. J. J Biol Chem 2003, 278, 40317-40323), which appears to be more flexible than the beta-strands based on disorder in the ensemble of calculated structures. Analogues of MrIA with N-terminal truncations indicate that the N-terminal residues play a role in defining a stable conformation and the native disulfide connectivity. In particular, noncovalent interactions between Val3 and Hyp12 are likely to be involved in maintaining a stable conformation. The N-terminus also affects activity, as a single N-terminal deletion introduced additional pharmacology at rat vas deferens, while deleting the first two amino acids reduced chi-conopeptide potency.

Solution structure of chi-conopeptide MrIA, a modulator of the human norepinephrine transporter.,Nilsson KP, Lovelace ES, Caesar CE, Tynngard N, Alewood PF, Johansson HM, Sharpe IA, Lewis RJ, Daly NL, Craik DJ Biopolymers. 2005;80(6):815-23. PMID:15931669^[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
↑ Nilsson KP, Lovelace ES, Caesar CE, Tynngard N, Alewood PF, Johansson HM, Sharpe IA, Lewis RJ, Daly NL, Craik DJ. Solution structure of chi-conopeptide MrIA, a modulator of the human norepinephrine transporter. Biopolymers. 2005;80(6):815-23. PMID:15931669 doi:10.1002/bip.20302

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/2ew4"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2ew4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_marmoreus Conus marmoreus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EW4 FirstGlance]. <br>
-</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=2ew4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ew4 OCA], [https://pdbe.org/2ew4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ew4 RCSB], [https://www.ebi.ac.uk/pdbsum/2ew4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ew4 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/CTA1A_CONMR CTA1A_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/CTA1A_CONMR CTA1A_CONMR] Chi-conotoxins inhibit the neuronal noradrenaline transporter (NET/SLC6A2) (PubMed:11528421, PubMed:12837768, PubMed:12885787, PubMed:16154696). Activity has been described on both human (inhibition of norepinephrine uptake is IC(50)=1.26 uM) and rat (pIC(50)=6.21 corresponding IC(50)=0.16 uM) transporters (PubMed:11528421, PubMed:12885787). Acts as a reversible non-competitive inhibitor (PubMed:11528421).<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 ==

2ew4

From Proteopedia

Current revision

Solution structure of MrIA

Structural highlights

Function

Publication Abstract from PubMed

References

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