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2mub

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Revision as of 08:51, 11 September 2015

Solution structure of the analgesic sea anemone peptide APETx2

Structural highlights

2mub is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1wxn
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[APT2_ANTEL] Potently and selectively blocks the acid-sensing ion channel ASIC3 (ACCN3). The blockade is rapid and reversible. Also inhibits heteromeric ASIC2b-ASIC3 (ACCN1-ACCN3) channel, while it has less affinity for ASIC1b-ASIC3 (ACCN2-ACCN3), ASIC1a-ASIC3 (ACCN2-ASIC3).^[1]

Publication Abstract from PubMed

The sea anemone peptide APETx2 is a potent and selective blocker of acid-sensing ion channel 3 (ASIC3). APETx2 is analgesic in a variety of rodent pain models, but the lack of knowledge of its pharmacophore and binding site on ASIC3 has impeded development of improved analogues. Here we present a detailed structure-activity relationship study of APETx2. Determination of a high-resolution structure of APETx2 combined with scanning mutagenesis revealed a cluster of aromatic and basic residues that mediate its interaction with ASIC3. We show that APETx2 also inhibits the off-target hERG channel by reducing the maximal current amplitude and shifting the voltage dependence of activation to more positive potentials. Electrophysiological screening of selected APETx2 mutants revealed partial overlap between the surfaces on APETx2 that mediate its interaction with ASIC3 and hERG. Characterization of the molecular basis of these interactions is an important first step toward the rational design of more selective APETx2 analogues.

Understanding the Molecular Basis of Toxin Promiscuity: The Analgesic Sea Anemone Peptide APETx2 Interacts with Acid-Sensing Ion Channel 3 and hERG Channels via Overlapping Pharmacophores.,Jensen JE, Cristofori-Armstrong B, Anangi R, Rosengren KJ, Lau CH, Mobli M, Brust A, Alewood PF, King GF, Rash LD J Med Chem. 2014 Nov 13;57(21):9195-203. doi: 10.1021/jm501400p. Epub 2014 Nov 4. PMID:25337890^[2]

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

References

↑ Diochot S, Baron A, Rash LD, Deval E, Escoubas P, Scarzello S, Salinas M, Lazdunski M. A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons. EMBO J. 2004 Apr 7;23(7):1516-25. Epub 2004 Mar 25. PMID:15044953 doi:http://dx.doi.org/10.1038/sj.emboj.7600177
↑ Jensen JE, Cristofori-Armstrong B, Anangi R, Rosengren KJ, Lau CH, Mobli M, Brust A, Alewood PF, King GF, Rash LD. Understanding the Molecular Basis of Toxin Promiscuity: The Analgesic Sea Anemone Peptide APETx2 Interacts with Acid-Sensing Ion Channel 3 and hERG Channels via Overlapping Pharmacophores. J Med Chem. 2014 Nov 13;57(21):9195-203. doi: 10.1021/jm501400p. Epub 2014 Nov 4. PMID:25337890 doi:http://dx.doi.org/10.1021/jm501400p

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/2mub"

@@ Line 4: / Line 4: @@
 <table><tr><td colspan='2'>[[2mub]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MUB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MUB FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wxn|1wxn]]</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=2mub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mub OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2mub RCSB], [http://www.ebi.ac.uk/pdbsum/2mub PDBsum]</span></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=2mub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mub OCA], [http://pdbe.org/2mub PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mub RCSB], [http://www.ebi.ac.uk/pdbsum/2mub PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2mub" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2mub

From Proteopedia

Revision as of 08:51, 11 September 2015

Solution structure of the analgesic sea anemone peptide APETx2

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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