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dc.contributor.authorAndreas, Loren
dc.contributor.authorEddy, Matthew Thomas
dc.contributor.authorPielak, Rafal M.
dc.contributor.authorChou, James
dc.contributor.authorGriffin, Robert Guy
dc.date.accessioned2012-08-03T13:42:02Z
dc.date.available2012-08-03T13:42:02Z
dc.date.issued2010-07
dc.date.submitted2010-02
dc.identifier.issn0002-7863
dc.identifier.issn1520-5126
dc.identifier.urihttp://hdl.handle.net/1721.1/71972
dc.description.abstractThe tetrameric M2 proton channel from influenza A virus conducts protons at low pH and is inhibited by aminoadamantyl drugs such as amantadine and rimantadine (Rmt). We report magic angle spinning NMR spectra of POPC and DPhPC membrane-embedded M2[subscript 18−60], both apo and in the presence of Rmt. Similar line widths in the spectra of apo and bound M2 indicate that Rmt does not have a significant impact on the dynamics or conformational heterogeneity of this construct. Substantial chemical shift changes for many residues in the transmembrane region support an allosteric mechanism of inhibition. An Rmt titration supports a binding stoichiometry of >1 Rmt molecule per channel and shows that nonspecific binding or changes in membrane composition are unlikely sources of the chemical shift changes. In addition, doubling of spectral lines in all of the observed samples provides evidence that the channel assembles with twofold symmetry.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (EB001960)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (EB002026)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Al067438)en_US
dc.description.sponsorshipNational Science Foundation (U.S.). Graduate Research Fellowship Programen_US
dc.language.isoen_US
dc.publisherAmerican Chemical Society (ACS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1021/ja101537pen_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePMCen_US
dc.titleMagic Angle Spinning NMR Investigation of Influenza A M2(18-60): Support for an Allosteric Mechanism of Inhibitionen_US
dc.typeArticleen_US
dc.identifier.citationAndreas, Loren B. et al. “Magic Angle Spinning NMR Investigation of Influenza A M2[subscript 18−60]: Support for an Allosteric Mechanism of Inhibition.” Journal of the American Chemical Society 132.32 (2010): 10958–10960.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.departmentFrancis Bitter Magnet Laboratory (Massachusetts Institute of Technology)en_US
dc.contributor.approverGriffin, Robert Guy
dc.contributor.mitauthorEddy, Matthew Thomas
dc.contributor.mitauthorGriffin, Robert Guy
dc.contributor.mitauthorAndreas, Loren
dc.relation.journalJournal of the American Chemical Societyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsAndreas, Loren B.; Eddy, Matthew T.; Pielak, Rafal M.; Chou, James; Griffin, Robert G.en
dc.identifier.orcidhttps://orcid.org/0000-0002-3349-6212
dc.identifier.orcidhttps://orcid.org/0000-0003-1589-832X
mit.licensePUBLISHER_POLICYen_US


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