2ew4

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[[Image:2ew4.png|left|200px]]
 
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{{STRUCTURE_2ew4| PDB=2ew4 | SCENE= }}
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==Solution structure of MrIA==
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<StructureSection load='2ew4' size='340' side='right'caption='[[2ew4]]' scene=''>
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== Structural highlights ==
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<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>
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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, 20 models</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=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
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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=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>
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</table>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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===Solution structure of MrIA===
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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<ref>PMID:15931669</ref>
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{{ABSTRACT_PUBMED_15931669}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 2ew4" style="background-color:#fffaf0;"></div>
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[[2ew4]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EW4 OCA].
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== References ==
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<references/>
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==Reference==
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__TOC__
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<ref group="xtra">PMID:015931669</ref><references group="xtra"/>
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</StructureSection>
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[[Category: Alewood, P F.]]
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[[Category: Conus marmoreus]]
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[[Category: Caesar, C E.]]
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[[Category: Large Structures]]
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[[Category: Craik, D J.]]
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[[Category: Alewood PF]]
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[[Category: Daly, N L.]]
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[[Category: Caesar CE]]
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[[Category: Johansson, H M.]]
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[[Category: Craik DJ]]
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[[Category: Lewis, R J.]]
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[[Category: Daly NL]]
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[[Category: Lovelace, E S.]]
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[[Category: Johansson HM]]
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[[Category: Nilsson, K P.]]
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[[Category: Lewis RJ]]
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[[Category: Sharpe, I A.]]
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[[Category: Lovelace ES]]
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[[Category: Tynngard, N.]]
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[[Category: Nilsson KP]]
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[[Category: Beta hairpin]]
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[[Category: Sharpe IA]]
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[[Category: Gamma turn]]
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[[Category: Tynngard N]]
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[[Category: Toxin]]
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Current revision

Solution structure of MrIA

PDB ID 2ew4

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