Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex
Ribonucleotide reductases (RNRs) are a diverse family of enzymes that are alone capable of generating 2'-deoxynucleotides de novo and are thus critical in DNA biosynthesis and repair. The nucleotide reduction reaction in all RNRs requires the generation of a transient active site thiyl radical,...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2020-04, Vol.368 (6489), p.424-427 |
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| creator | Kang, Gyunghoon Taguchi, Alexander T Stubbe, JoAnne Drennan, Catherine L |
| description | Ribonucleotide reductases (RNRs) are a diverse family of enzymes that are alone capable of generating 2'-deoxynucleotides de novo and are thus critical in DNA biosynthesis and repair. The nucleotide reduction reaction in all RNRs requires the generation of a transient active site thiyl radical, and in class I RNRs, this process involves a long-range radical transfer between two subunits, α and β. Because of the transient subunit association, an atomic resolution structure of an active α2β2 RNR complex has been elusive. We used a doubly substituted β2, E52Q/(2,3,5)-trifluorotyrosine122-β2, to trap wild-type α2 in a long-lived α2β2 complex. We report the structure of this complex by means of cryo-electron microscopy to 3.6-angstrom resolution, allowing for structural visualization of a 32-angstrom-long radical transfer pathway that affords RNR activity. |
| doi_str_mv | 10.1126/science.aba6794 |
| format | Article |
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The nucleotide reduction reaction in all RNRs requires the generation of a transient active site thiyl radical, and in class I RNRs, this process involves a long-range radical transfer between two subunits, α and β. Because of the transient subunit association, an atomic resolution structure of an active α2β2 RNR complex has been elusive. We used a doubly substituted β2, E52Q/(2,3,5)-trifluorotyrosine122-β2, to trap wild-type α2 in a long-lived α2β2 complex. 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| subjects | Biocatalysis Biosynthesis Catalytic Domain Cryoelectron Microscopy Deoxyribonucleic acid DNA Electron microscopy Escherichia coli Proteins - chemistry Escherichia coli Proteins - genetics Holoenzymes - chemistry Holoenzymes - genetics Microscopy Protein Conformation Reductase Reductases Ribonucleotide reductase Ribonucleotide Reductases - chemistry Ribonucleotide Reductases - genetics Tyrosine - chemistry Visualization |
| title | Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex |
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