Computational Approaches: An Underutilized Tool in the Quest to Elucidate Radical SAM Dynamics

Davis, Katherine M.

doi:10.3390/molecules26092590

“…An acetyl radical may then be formed and attached at the C5 position of U34. In Figure 7, the related Escherichia coli enzyme RlmN methylase is shown that modifies the 2-carbon of tRNA-A37 [73,74]. The RlmN images were selected because they better emphasize some properties of these ancient enzymes.…”

Section: Trna Modifications Are As Old As Lucamentioning

confidence: 99%

“Superwobbling” and tRNA-34 Wobble and tRNA-37 Anticodon Loop Modifications in Evolution and Devolution of the Genetic Code

Lei

¹

,

Burton

²

2022

Life

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The genetic code evolved around the reading of the tRNA anticodon on the primitive ribosome, and tRNA-34 wobble and tRNA-37 modifications coevolved with the code. We posit that EF-Tu, the closing mechanism of the 30S ribosomal subunit, methylation of wobble U34 at the 5-carbon and suppression of wobbling at the tRNA-36 position were partly redundant and overlapping functions that coevolved to establish the code. The genetic code devolved in evolution of mitochondria to reduce the size of the tRNAome (all of the tRNAs of an organism or organelle). “Superwobbling” or four-way wobbling describes a major mechanism for shrinking the mitochondrial tRNAome. In superwobbling, unmodified wobble tRNA-U34 can recognize all four codon wobble bases (A, G, C and U), allowing a single unmodified tRNA-U34 to read a 4-codon box. During code evolution, to suppress superwobbling in 2-codon sectors, U34 modification by methylation at the 5-carbon position appears essential. As expected, at the base of code evolution, tRNA-37 modifications mostly related to the identity of the adjacent tRNA-36 base. TRNA-37 modifications help maintain the translation frame during elongation.

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“…, through computational modeling. 70 Such approaches lend themselves to screening, with a rapid set of modifications being enabled and tested ( Figure 8 ). An important factor is how to and what to screen these systems for.…”

Section: Computational Approaches To Screeningmentioning

confidence: 99%

If It Is Hard, It Is Worth Doing: Engineering Radical Enzymes from Anaerobes

Jäger

¹

,

Croft

²

2022

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With a pressing need for sustainable chemistries, radical enzymes from anaerobes offer a shortcut for many chemical transformations and deliver highly sought-after functionalizations such as late-stage C–H functionalization, C–C bond formation, and carbon-skeleton rearrangements, among others. The challenges in handling these oxygen-sensitive enzymes are reflected in their limited industrial exploitation, despite what they may deliver. With an influx of structures and mechanistic understanding, the scope for designed radical enzymes to deliver wanted processes becomes ever closer. Combined with new advances in computational methods and workflows for these complex systems, the outlook for an increased use of radical enzymes in future processes is exciting.

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“…An acetyl radical may then be formed and attached at the C5 position of U34. In Figure 7, the related E. coli enzyme RlmN methylase is shown that modifies the 2-carbon of tRNA-A37 [72,73]. The RlmN images were selected because they better emphasize some properties of these ancient enzymes.…”

Section: Trna Modifications Are As Old As Lucamentioning

confidence: 99%

“Superwobbling” and tRNA-34 wobble and tRNA-37 anticodon loop modifications in evolution and devolution of the genetic code

Lei¹,

Burton²

2022

Preprint

4

0

View full text Add to dashboard Cite

The genetic code evolved around the reading of the tRNA anticodon on the primitive ribosome, and tRNA-34 wobble and tRNA-37 modifications coevolved with the code. We posit that EF-Tu, the closing mechanism of the 30S ribosomal subunit, methylation of wobble U34 at the 5-carbon and suppression of wobbling at the tRNA-36 position were partly redundant and overlapping functions that coevolved to establish the code. The genetic code devolved in evolution of mitochondria to reduce the size of the tRNAome (all of the tRNAs of an organism or organelle). “Superwobbling” or four-way wobbling describes a major mechanism for shrinking the mitochondrial tRNAome. In superwobbling, unmodified wobble tRNA-U34 can recognize all four codon wobble bases (A, G, C and U), allowing a single unmodified tRNA-U34 to read a 4-codon box. During code evolution, to suppress superwobbling in 2-codon sectors, U34 modification by methylation at the 5-carbon position appears essential. As expected, at the base of code evolution, tRNA-37 modifications mostly related to the identity of the adjacent tRNA-36 base. TRNA-37 modifications help maintain the translation frame during elongation.

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Computational Approaches: An Underutilized Tool in the Quest to Elucidate Radical SAM Dynamics

Cited by 7 publications

References 62 publications

“Superwobbling” and tRNA-34 Wobble and tRNA-37 Anticodon Loop Modifications in Evolution and Devolution of the Genetic Code

“Superwobbling” and tRNA-34 Wobble and tRNA-37 Anticodon Loop Modifications in Evolution and Devolution of the Genetic Code

If It Is Hard, It Is Worth Doing: Engineering Radical Enzymes from Anaerobes

“Superwobbling” and tRNA-34 wobble and tRNA-37 anticodon loop modifications in evolution and devolution of the genetic code

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