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In the current study we have determined the solution structure of MrIA using NMR spectroscopy. The major element of secondary structure is a <jats:italic>\u03b2<\/jats:italic>\u2010hairpin with the two strands connected by an inverse \u03b3\u2010turn. 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\u201340323), which appears to be more flexible than the <jats:italic>\u03b2<\/jats:italic>\u2010strands based on disorder in the ensemble of calculated structures. Analogues of MrIA with N\u2010terminal truncations indicate that the N\u2010terminal 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\u2010terminus also affects activity, as a single N\u2010terminal deletion introduced additional pharmacology at rat vas deferens, while deleting the first two amino acids reduced \u03c7\u2010conopeptide potency. \u00a9 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 80: 815\u2013823, 2005<\/jats:p><jats:p>This article was originally published online as an accepted preprint. The \u201cPublished Online\u201d date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com<\/jats:p>","DOI":"10.1002\/bip.20302","type":"journal-article","created":{"date-parts":[[2005,6,1]],"date-time":"2005-06-01T18:47:00Z","timestamp":1117651620000},"page":"815-823","source":"Crossref","is-referenced-by-count":39,"title":["Solution structure of \u03c7\u2010conopeptide MrIA, a modulator of the human norepinephrine transporter"],"prefix":"10.1002","volume":"80","author":[{"given":"K. 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