Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli
Ribonucleotide reductase (RNR) converts ribonucleotides to deoxyribonucleotides, a reaction that is essential for DNA biosynthesis and repair. This enzyme is responsible for reducing all four ribonucleotide substrates, with specificity regulated by the binding of an effector to a distal allosteric s...
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| Format: | Article |
| Language: | en_US |
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eLife Sciences Publications, Ltd.
2016
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| Online Access: | http://hdl.handle.net/1721.1/101398 https://orcid.org/0000-0001-5486-2755 https://orcid.org/0000-0001-7362-9801 https://orcid.org/0000-0003-2117-3528 |
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| author | Kang, Gyung Hoon Chen, Yang-Ting Zimanyi, Christina Marie Funk, Michael Andrew Drennan, Catherine L |
| author2 | Massachusetts Institute of Technology. Center for Environmental Health Sciences |
| author_facet | Massachusetts Institute of Technology. Center for Environmental Health Sciences Kang, Gyung Hoon Chen, Yang-Ting Zimanyi, Christina Marie Funk, Michael Andrew Drennan, Catherine L |
| author_sort | Kang, Gyung Hoon |
| collection | MIT |
| description | Ribonucleotide reductase (RNR) converts ribonucleotides to deoxyribonucleotides, a reaction that is essential for DNA biosynthesis and repair. This enzyme is responsible for reducing all four ribonucleotide substrates, with specificity regulated by the binding of an effector to a distal allosteric site. In all characterized RNRs, the binding of effector dATP alters the active site to select for pyrimidines over purines, whereas effectors dGTP and TTP select for substrates ADP and GDP, respectively. Here, we have determined structures of Escherichia coli class Ia RNR with all four substrate/specificity effector-pairs bound (CDP/dATP, UDP/dATP, ADP/dGTP, GDP/TTP) that reveal the conformational rearrangements responsible for this remarkable allostery. These structures delineate how RNR ‘reads’ the base of each effector and communicates substrate preference to the active site by forming differential hydrogen bonds, thereby maintaining the proper balance of deoxynucleotides in the cell. |
| first_indexed | 2024-09-23T16:46:08Z |
| format | Article |
| id | mit-1721.1/101398 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:46:08Z |
| publishDate | 2016 |
| publisher | eLife Sciences Publications, Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/1013982022-09-29T21:22:32Z Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli Kang, Gyung Hoon Chen, Yang-Ting Zimanyi, Christina Marie Funk, Michael Andrew Drennan, Catherine L Massachusetts Institute of Technology. Center for Environmental Health Sciences Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Zimanyi, Christina M. Chen, Percival Yang-Ting Kang, Gyung Hoon Funk, Michael A. Drennan, Catherine L. Ribonucleotide reductase (RNR) converts ribonucleotides to deoxyribonucleotides, a reaction that is essential for DNA biosynthesis and repair. This enzyme is responsible for reducing all four ribonucleotide substrates, with specificity regulated by the binding of an effector to a distal allosteric site. In all characterized RNRs, the binding of effector dATP alters the active site to select for pyrimidines over purines, whereas effectors dGTP and TTP select for substrates ADP and GDP, respectively. Here, we have determined structures of Escherichia coli class Ia RNR with all four substrate/specificity effector-pairs bound (CDP/dATP, UDP/dATP, ADP/dGTP, GDP/TTP) that reveal the conformational rearrangements responsible for this remarkable allostery. These structures delineate how RNR ‘reads’ the base of each effector and communicates substrate preference to the active site by forming differential hydrogen bonds, thereby maintaining the proper balance of deoxynucleotides in the cell. National Institutes of Health (U.S.) (Grant T32GM08334) National Institutes of Health (U.S.) (Grant P30-ES002109) National Science Foundation (U.S.). Graduate Research Fellowship (Grant 0645960) 2016-03-02T02:46:35Z 2016-03-02T02:46:35Z 2016-01 2015-02 Article http://purl.org/eprint/type/JournalArticle 2050-084X http://hdl.handle.net/1721.1/101398 Zimanyi, Christina M, Percival Yang-Ting Chen, Gyunghoon Kang, Michael A Funk, and Catherine L Drennan. “Molecular Basis for Allosteric Specificity Regulation in Class Ia Ribonucleotide Reductase from Escherichia Coli.” eLife 5 (January 12, 2016). https://orcid.org/0000-0001-5486-2755 https://orcid.org/0000-0001-7362-9801 https://orcid.org/0000-0003-2117-3528 en_US http://dx.doi.org/10.7554/eLife.07141 eLife Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd. eLife Sciences Publications, Ltd. |
| spellingShingle | Kang, Gyung Hoon Chen, Yang-Ting Zimanyi, Christina Marie Funk, Michael Andrew Drennan, Catherine L Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli |
| title | Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli |
| title_full | Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli |
| title_fullStr | Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli |
| title_full_unstemmed | Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli |
| title_short | Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli |
| title_sort | molecular basis for allosteric specificity regulation in class ia ribonucleotide reductase from escherichia coli |
| url | http://hdl.handle.net/1721.1/101398 https://orcid.org/0000-0001-5486-2755 https://orcid.org/0000-0001-7362-9801 https://orcid.org/0000-0003-2117-3528 |
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