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2ew4

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[[Image:2ew4.gif|left|200px]]
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{{Seed}}
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{{STRUCTURE_2ew4| PDB=2ew4 | SCENE= }}
{{STRUCTURE_2ew4| PDB=2ew4 | SCENE= }}
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'''Solution structure of MrIA'''
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===Solution structure of MrIA===
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==Overview==
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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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The line below this paragraph, {{ABSTRACT_PUBMED_15931669}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15931669 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15931669}}
==About this Structure==
==About this Structure==
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Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EW4 OCA].
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Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EW4 OCA].
==Reference==
==Reference==
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[[Category: Beta hairpin]]
[[Category: Beta hairpin]]
[[Category: Gamma turn]]
[[Category: Gamma turn]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:10:52 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:40:51 2008''

Revision as of 04:40, 29 July 2008

Image:2ew4.png

Template:STRUCTURE 2ew4

Solution structure of MrIA

Template:ABSTRACT PUBMED 15931669

About this Structure

Full experimental information is available from OCA.

Reference

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

Page seeded by OCA on Tue Jul 29 07:40:51 2008

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