New tricks for the glycyl radical enzyme family
Glycyl radical enzymes (GREs) are important biological catalysts in both strict and facultative anaerobes, playing key roles both in the human microbiota and in the environment. GREs contain a backbone glycyl radical that is post-translationally installed, enabling radical-based mechanisms. GREs fun...
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| Format: | Article |
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Informa UK Limited
2018
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| Online Access: | http://hdl.handle.net/1721.1/116351 https://orcid.org/0000-0002-0323-1336 https://orcid.org/0000-0002-7680-0173 https://orcid.org/0000-0001-5486-2755 |
| _version_ | 1826215124357087232 |
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| author | Funk, Michael A. Backman, Lindsey R. Dawson, Christopher Daniel Drennan, Catherine L. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Funk, Michael A. Backman, Lindsey R. Dawson, Christopher Daniel Drennan, Catherine L. |
| author_sort | Funk, Michael A. |
| collection | MIT |
| description | Glycyl radical enzymes (GREs) are important biological catalysts in both strict and facultative anaerobes, playing key roles both in the human microbiota and in the environment. GREs contain a backbone glycyl radical that is post-translationally installed, enabling radical-based mechanisms. GREs function in several metabolic pathways including mixed acid fermentation, ribonucleotide reduction and the anaerobic breakdown of the nutrient choline and the pollutant toluene. By generating a substrate-based radical species within the active site, GREs enable C–C, C–O and C–N bond breaking and formation steps that are otherwise challenging for nonradical enzymes. Identification of previously unknown family members from genomic data and the determination of structures of well-characterized GREs have expanded the scope of GRE-catalyzed reactions as well as defined key features that enable radical catalysis. Here, we review the structures and mechanisms of characterized GREs, classifying members into five categories. We consider the open questions about each of the five GRE classes and evaluate the tools available to interrogate uncharacterized GREs. Keywords: Glycyl radical enzymes; radical chemistry; anaerobic metabolism; pyruvate formate-lyase; class III ribonucleotide reductase; choline trimethylamine-lyase; benzylsuccinate synthase; radical decarboxylases |
| first_indexed | 2024-09-23T16:16:56Z |
| format | Article |
| id | mit-1721.1/116351 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:16:56Z |
| publishDate | 2018 |
| publisher | Informa UK Limited |
| record_format | dspace |
| spelling | mit-1721.1/1163512022-10-02T07:33:23Z New tricks for the glycyl radical enzyme family Funk, Michael A. Backman, Lindsey R. Dawson, Christopher Daniel Drennan, Catherine L. Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Backman, Lindsey R. Dawson, Christopher Daniel Drennan, Catherine L. Glycyl radical enzymes (GREs) are important biological catalysts in both strict and facultative anaerobes, playing key roles both in the human microbiota and in the environment. GREs contain a backbone glycyl radical that is post-translationally installed, enabling radical-based mechanisms. GREs function in several metabolic pathways including mixed acid fermentation, ribonucleotide reduction and the anaerobic breakdown of the nutrient choline and the pollutant toluene. By generating a substrate-based radical species within the active site, GREs enable C–C, C–O and C–N bond breaking and formation steps that are otherwise challenging for nonradical enzymes. Identification of previously unknown family members from genomic data and the determination of structures of well-characterized GREs have expanded the scope of GRE-catalyzed reactions as well as defined key features that enable radical catalysis. Here, we review the structures and mechanisms of characterized GREs, classifying members into five categories. We consider the open questions about each of the five GRE classes and evaluate the tools available to interrogate uncharacterized GREs. Keywords: Glycyl radical enzymes; radical chemistry; anaerobic metabolism; pyruvate formate-lyase; class III ribonucleotide reductase; choline trimethylamine-lyase; benzylsuccinate synthase; radical decarboxylases National Institutes of Health (U.S.) (Grant GM069857) National Institutes of Health (U.S.) (Grant T32GM007287) National Science Foundation (U.S.) (Grant 1122374) 2018-06-15T19:34:45Z 2018-06-15T19:34:45Z 2017-09 2017-05 2018-06-15T13:28:33Z Article http://purl.org/eprint/type/JournalArticle 1040-9238 1549-7798 http://hdl.handle.net/1721.1/116351 Backman, Lindsey R. F. et al. “New Tricks for the Glycyl Radical Enzyme Family.” Critical Reviews in Biochemistry and Molecular Biology 52, 6 (September 2017): 674–695 © 2017 Informa UK Limited, trading as Taylor & Francis Group https://orcid.org/0000-0002-0323-1336 https://orcid.org/0000-0002-7680-0173 https://orcid.org/0000-0001-5486-2755 http://dx.doi.org/10.1080/10409238.2017.1373741 Critical Reviews in Biochemistry and Molecular Biology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Informa UK Limited PMC |
| spellingShingle | Funk, Michael A. Backman, Lindsey R. Dawson, Christopher Daniel Drennan, Catherine L. New tricks for the glycyl radical enzyme family |
| title | New tricks for the glycyl radical enzyme family |
| title_full | New tricks for the glycyl radical enzyme family |
| title_fullStr | New tricks for the glycyl radical enzyme family |
| title_full_unstemmed | New tricks for the glycyl radical enzyme family |
| title_short | New tricks for the glycyl radical enzyme family |
| title_sort | new tricks for the glycyl radical enzyme family |
| url | http://hdl.handle.net/1721.1/116351 https://orcid.org/0000-0002-0323-1336 https://orcid.org/0000-0002-7680-0173 https://orcid.org/0000-0001-5486-2755 |
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