Redox-Linked Changes to the Hydrogen-Bonding Network of Ribonucleotide Reductase β2
Ribonucleotide reductase (RNR) catalyzes conversion of nucleoside diphosphates (NDPs) to 2′-deoxynucleotides, a critical step in DNA replication and repair in all organisms. Class-Ia RNRs, found in aerobic bacteria and all eukaryotes, are a complex of two subunits: α2 and β2. The β2 subunit contains...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2015
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| Online Access: | http://hdl.handle.net/1721.1/95666 https://orcid.org/0000-0001-8076-4489 |
| _version_ | 1811076039359594496 |
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| author | Offenbacher, Adam R. Minnihan, Ellen Catherine Stubbe, JoAnne Barry, Bridgette A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Offenbacher, Adam R. Minnihan, Ellen Catherine Stubbe, JoAnne Barry, Bridgette A. |
| author_sort | Offenbacher, Adam R. |
| collection | MIT |
| description | Ribonucleotide reductase (RNR) catalyzes conversion of nucleoside diphosphates (NDPs) to 2′-deoxynucleotides, a critical step in DNA replication and repair in all organisms. Class-Ia RNRs, found in aerobic bacteria and all eukaryotes, are a complex of two subunits: α2 and β2. The β2 subunit contains an essential diferric–tyrosyl radical (Y122O•) cofactor that is needed to initiate reduction of NDPs in the α2 subunit. In this work, we investigated the Y122O• reduction mechanism in Escherichia coli β2 by hydroxyurea (HU), a radical scavenger and cancer therapeutic agent. We tested the hypothesis that Y122OH redox reactions cause structural changes in the diferric cluster. Reduction of Y122O• was studied using reaction-induced FT-IR spectroscopy and [[superscript 13]C]aspartate-labeled β2. These Y122O• minus Y122OH difference spectra provide evidence that the Y122OH redox reaction is associated with a frequency change to the asymmetric vibration of D84, a unidentate ligand to the diferric cluster. The results are consistent with a redox-induced shift in H-bonding between Y122OH and D84 that may regulate proton-transfer reactions on the HU-mediated inactivation pathway in isolated β2. |
| first_indexed | 2024-09-23T10:15:08Z |
| format | Article |
| id | mit-1721.1/95666 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:15:08Z |
| publishDate | 2015 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/956662022-09-26T16:42:54Z Redox-Linked Changes to the Hydrogen-Bonding Network of Ribonucleotide Reductase β2 Offenbacher, Adam R. Minnihan, Ellen Catherine Stubbe, JoAnne Barry, Bridgette A. Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Stubbe, JoAnne Minnihan, Ellen Catherine Ribonucleotide reductase (RNR) catalyzes conversion of nucleoside diphosphates (NDPs) to 2′-deoxynucleotides, a critical step in DNA replication and repair in all organisms. Class-Ia RNRs, found in aerobic bacteria and all eukaryotes, are a complex of two subunits: α2 and β2. The β2 subunit contains an essential diferric–tyrosyl radical (Y122O•) cofactor that is needed to initiate reduction of NDPs in the α2 subunit. In this work, we investigated the Y122O• reduction mechanism in Escherichia coli β2 by hydroxyurea (HU), a radical scavenger and cancer therapeutic agent. We tested the hypothesis that Y122OH redox reactions cause structural changes in the diferric cluster. Reduction of Y122O• was studied using reaction-induced FT-IR spectroscopy and [[superscript 13]C]aspartate-labeled β2. These Y122O• minus Y122OH difference spectra provide evidence that the Y122OH redox reaction is associated with a frequency change to the asymmetric vibration of D84, a unidentate ligand to the diferric cluster. The results are consistent with a redox-induced shift in H-bonding between Y122OH and D84 that may regulate proton-transfer reactions on the HU-mediated inactivation pathway in isolated β2. National Institutes of Health (U.S.) (Grant GM29595) 2015-02-26T18:02:47Z 2015-02-26T18:02:47Z 2013-04 2012-04 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/95666 Offenbacher, Adam R., Ellen C. Minnihan, JoAnne Stubbe, and Bridgette A. Barry. “Redox-Linked Changes to the Hydrogen-Bonding Network of Ribonucleotide Reductase Β2.” Journal of the American Chemical Society 135, no. 17 (May 2013): 6380–6383. https://orcid.org/0000-0001-8076-4489 en_US http://dx.doi.org/10.1021/ja3032949 Journal of the American Chemical Society Article 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. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Offenbacher, Adam R. Minnihan, Ellen Catherine Stubbe, JoAnne Barry, Bridgette A. Redox-Linked Changes to the Hydrogen-Bonding Network of Ribonucleotide Reductase β2 |
| title | Redox-Linked Changes to the Hydrogen-Bonding Network of Ribonucleotide Reductase β2 |
| title_full | Redox-Linked Changes to the Hydrogen-Bonding Network of Ribonucleotide Reductase β2 |
| title_fullStr | Redox-Linked Changes to the Hydrogen-Bonding Network of Ribonucleotide Reductase β2 |
| title_full_unstemmed | Redox-Linked Changes to the Hydrogen-Bonding Network of Ribonucleotide Reductase β2 |
| title_short | Redox-Linked Changes to the Hydrogen-Bonding Network of Ribonucleotide Reductase β2 |
| title_sort | redox linked changes to the hydrogen bonding network of ribonucleotide reductase β2 |
| url | http://hdl.handle.net/1721.1/95666 https://orcid.org/0000-0001-8076-4489 |
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