dc.contributor.author | Brignole, Edward J | |
dc.contributor.author | Tsai, Kuang-Lei | |
dc.contributor.author | Chittuluru, Johnathan | |
dc.contributor.author | Li, Haoran | |
dc.contributor.author | Aye, Yimon | |
dc.contributor.author | Penczek, Pawel A | |
dc.contributor.author | Stubbe, JoAnne | |
dc.contributor.author | Drennan, Catherine L. | |
dc.contributor.author | Asturias, Francisco | |
dc.date.accessioned | 2018-04-24T17:34:49Z | |
dc.date.available | 2018-04-24T17:34:49Z | |
dc.date.issued | 2018-02 | |
dc.date.submitted | 2017-08 | |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | http://hdl.handle.net/1721.1/114937 | |
dc.description.abstract | Ribonucleotide 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.sponsorship | National Institutes of Health (U.S.) (Grant GM29595) | en_US |
dc.publisher | eLife Sciences Publications, Ltd | en_US |
dc.relation.isversionof | http://dx.doi.org/10.7554/eLife.31502 | en_US |
dc.rights | Creative Commons Attribution 4.0 International License | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_US |
dc.source | eLife | en_US |
dc.title | 3.3-Å resolution cryo-EM structure of human ribonucleotide reductase with substrate and allosteric regulators bound | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Brignole, 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 al | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemistry | en_US |
dc.contributor.mitauthor | Brignole, Edward J | |
dc.contributor.mitauthor | Stubbe, JoAnne | |
dc.contributor.mitauthor | Drennan, Catherine L. | |
dc.relation.journal | eLife | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2018-04-20T19:01:01Z | |
dspace.orderedauthors | Brignole, Edward J; Tsai, Kuang-Lei; Chittuluru, Johnathan; Li, Haoran; Aye, Yimon; Penczek, Pawel A; Stubbe, JoAnne; Drennan, Catherine L; Asturias, Francisco | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-4285-6128 | |
dc.identifier.orcid | https://orcid.org/0000-0001-8076-4489 | |
dc.identifier.orcid | https://orcid.org/0000-0001-5486-2755 | |
dspace.mitauthor.error | true | |
mit.license | PUBLISHER_CC | en_US |