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dc.contributor.authorBrignole, Edward J
dc.contributor.authorTsai, Kuang-Lei
dc.contributor.authorChittuluru, Johnathan
dc.contributor.authorLi, Haoran
dc.contributor.authorAye, Yimon
dc.contributor.authorPenczek, Pawel A
dc.contributor.authorStubbe, JoAnne
dc.contributor.authorDrennan, Catherine L.
dc.contributor.authorAsturias, Francisco
dc.date.accessioned2018-04-24T17:34:49Z
dc.date.available2018-04-24T17:34:49Z
dc.date.issued2018-02
dc.date.submitted2017-08
dc.identifier.issn2050-084X
dc.identifier.urihttp://hdl.handle.net/1721.1/114937
dc.description.abstractRibonucleotide reductases (RNRs) convert ribonucleotides into deoxyribonucleotides, a reaction essential for DNA replication and repair. Human RNR requires two subunits for activity, the α subunit contains the active site, and the β subunit houses the radical cofactor. Here, we present a 3.3-Å resolution structure by cryo-electron microscopy (EM) of a dATP-inhibited state of human RNR. This structure, which was determined in the presence of substrate CDP and allosteric regulators ATP and dATP, has three α 2 units arranged in an α 6 ring. At near-atomic resolution, these data provide insight into the molecular basis for CDP recognition by allosteric specificity effectors dATP/ATP. Additionally, we present lower-resolution EM structures of human α 6 in the presence of both the anticancer drug clofarabine triphosphate and β 2 . Together, these structures support a model for RNR inhibition in which β 2 is excluded from binding in a radical transfer competent position when α exists as a stable hexamer.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant GM29595)en_US
dc.publishereLife Sciences Publications, Ltden_US
dc.relation.isversionofhttp://dx.doi.org/10.7554/eLife.31502en_US
dc.rightsCreative Commons Attribution 4.0 International Licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceeLifeen_US
dc.title3.3-Å resolution cryo-EM structure of human ribonucleotide reductase with substrate and allosteric regulators bounden_US
dc.typeArticleen_US
dc.identifier.citationBrignole, Edward J et al. “3.3-Å Resolution Cryo-EM Structure of Human Ribonucleotide Reductase with Substrate and Allosteric Regulators Bound.” eLife 7 (February 2018): e31502 © Brignole et alen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.mitauthorBrignole, Edward J
dc.contributor.mitauthorStubbe, JoAnne
dc.contributor.mitauthorDrennan, Catherine L.
dc.relation.journaleLifeen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-04-20T19:01:01Z
dspace.orderedauthorsBrignole, Edward J; Tsai, Kuang-Lei; Chittuluru, Johnathan; Li, Haoran; Aye, Yimon; Penczek, Pawel A; Stubbe, JoAnne; Drennan, Catherine L; Asturias, Franciscoen_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-4285-6128
dc.identifier.orcidhttps://orcid.org/0000-0001-8076-4489
dc.identifier.orcidhttps://orcid.org/0000-0001-5486-2755
dspace.mitauthor.errortrue
mit.licensePUBLISHER_CCen_US


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