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dc.contributor.authorHu, SH
dc.contributor.authorLoughnan, M
dc.contributor.authorMiller, R
dc.contributor.authorWeeks, CM
dc.contributor.authorBlessing, RH
dc.contributor.authorAlewood, PF
dc.contributor.authorLewis, RJ
dc.contributor.authorMartin, JL
dc.date.accessioned2017-10-05T02:23:32Z
dc.date.available2017-10-05T02:23:32Z
dc.date.issued1998
dc.identifier.issn0006-2960
dc.identifier.doi10.1021/bi9806549
dc.identifier.urihttp://hdl.handle.net/10072/347899
dc.description.abstractConotoxins are valuable probes of receptors and ion channels because of their small size and highly selective activity. α-Conotoxin EpI, a 16-residue peptide from the mollusk-hunting Conus episcopatus, has the amino acid sequence GCCSDPRCNMNNPDY(SO3H)C-NH2 and appears to be an extremely potent and selective inhibitor of the α3β2 and α3β4 neuronal subtypes of the nicotinic acetylcholine receptor (nAChR). The desulfated form of EpI ([Tyr15]EpI) has a potency and selectivity for the nAChR receptor similar to those of EpI. Here we describe the crystal structure of [Tyr15]EpI solved at a resolution of 1.1 Å using SnB. The asymmetric unit has a total of 284 non-hydrogen atoms, making this one of the largest structures solved de novo by direct methods. The [Tyr15]EpI structure brings to six the number of α-conotoxin structures that have been determined to date. Four of these, [Tyr15]EpI, PnIA, PnIB, and MII, have an α4/7 cysteine framework and are selective for the neuronal subtype of the nAChR. The structure of [Tyr15]EpI has the same backbone fold as the other α4/7-conotoxin structures, supporting the notion that this conotoxin cysteine framework and spacing give rise to a conserved fold. The surface charge distribution of [Tyr15]EpI is similar to that of PnIA and PnIB but is likely to be different from that of MII, suggesting that [Tyr15]EpI and MII may have different binding modes for the same receptor subtype.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Chemical Society
dc.relation.ispartofpagefrom11425
dc.relation.ispartofpageto11433
dc.relation.ispartofissue33
dc.relation.ispartofjournalBiochemistry
dc.relation.ispartofvolume37
dc.subject.fieldofresearchMedicinal and biomolecular chemistry
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchBiochemistry and cell biology not elsewhere classified
dc.subject.fieldofresearchMedical biochemistry and metabolomics
dc.subject.fieldofresearchcode3404
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode310199
dc.subject.fieldofresearchcode3205
dc.titleThe 1.1 Å Resolution crystal structure of [Tyr15]EpI, a novel a-Conotoxin from Conus episcopatus, solved by direct methods
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorMartin, Jennifer


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