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The origin and evolution of ribonucleotide reduction.

Lundin D, Berggren G, Logan DT, Sjöberg BM - Life (Basel) (2015)

Bottom Line: Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms.This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR).While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR).

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden. daniel.lundin@scilifelab.se.

ABSTRACT
Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms. This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR). The mechanism has been deemed unlikely to be catalyzed by a ribozyme, creating an enigma regarding how the building blocks for DNA were synthesized at the transition from RNA- to DNA-encoded genomes. While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR). From the protoRNR evolved the ancestor to modern RNRs, the urRNR, which diversified into the modern three classes. Since the initial radical generation differs between the three modern classes, it is difficult to establish how it was generated in the urRNR. Here we suggest a model that is similar to the B12-dependent mechanism in modern class II RNRs.

No MeSH data available.


Model for the evolution of the modern three RNR classes from the common ancestor, the urRNR. Informative characteristics for the reconstruction have been indicated. The substrate is shown as a graphical representation of a ribonucleotide while the text “dNTP” in the dimer interface indicates effector nucleotides for substrate specificity regulation (ATP, not being a dNTP, is also an effector). Conserved disulfides in the active site as well as on the outside of the protein in class I and class II, the H-bonding carboxylate/base, and the various radical species are shown. The different radical-generating metal cofactors of the three classes are also shown as well as an “M” within a dashed circle indicating the metal center of the urRNR. See also Table 1.
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life-05-00604-f009: Model for the evolution of the modern three RNR classes from the common ancestor, the urRNR. Informative characteristics for the reconstruction have been indicated. The substrate is shown as a graphical representation of a ribonucleotide while the text “dNTP” in the dimer interface indicates effector nucleotides for substrate specificity regulation (ATP, not being a dNTP, is also an effector). Conserved disulfides in the active site as well as on the outside of the protein in class I and class II, the H-bonding carboxylate/base, and the various radical species are shown. The different radical-generating metal cofactors of the three classes are also shown as well as an “M” within a dashed circle indicating the metal center of the urRNR. See also Table 1.

Mentions: The presence of two cysteines involved in reduction together with the use of a protein reductant (glutaredoxin or thioredoxin) is thus shared by class I and II but not by a majority of class III RNRs, and when present in class III RNRs the mechanism is different to that in class I and II [46]. Combined, these observations suggest that class I and II are more closely related, as is also indicated by overall sequence similarity between classes. Furthermore, some of the β-strands taking part in B12 binding in class II are present in class I RNR [39], but not in class III (Figure 6). In line with this, we present a model for how class II and III diverged from the urRNR, and how class I diverged from class II RNR (Figure 9).


The origin and evolution of ribonucleotide reduction.

Lundin D, Berggren G, Logan DT, Sjöberg BM - Life (Basel) (2015)

Model for the evolution of the modern three RNR classes from the common ancestor, the urRNR. Informative characteristics for the reconstruction have been indicated. The substrate is shown as a graphical representation of a ribonucleotide while the text “dNTP” in the dimer interface indicates effector nucleotides for substrate specificity regulation (ATP, not being a dNTP, is also an effector). Conserved disulfides in the active site as well as on the outside of the protein in class I and class II, the H-bonding carboxylate/base, and the various radical species are shown. The different radical-generating metal cofactors of the three classes are also shown as well as an “M” within a dashed circle indicating the metal center of the urRNR. See also Table 1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390871&req=5

life-05-00604-f009: Model for the evolution of the modern three RNR classes from the common ancestor, the urRNR. Informative characteristics for the reconstruction have been indicated. The substrate is shown as a graphical representation of a ribonucleotide while the text “dNTP” in the dimer interface indicates effector nucleotides for substrate specificity regulation (ATP, not being a dNTP, is also an effector). Conserved disulfides in the active site as well as on the outside of the protein in class I and class II, the H-bonding carboxylate/base, and the various radical species are shown. The different radical-generating metal cofactors of the three classes are also shown as well as an “M” within a dashed circle indicating the metal center of the urRNR. See also Table 1.
Mentions: The presence of two cysteines involved in reduction together with the use of a protein reductant (glutaredoxin or thioredoxin) is thus shared by class I and II but not by a majority of class III RNRs, and when present in class III RNRs the mechanism is different to that in class I and II [46]. Combined, these observations suggest that class I and II are more closely related, as is also indicated by overall sequence similarity between classes. Furthermore, some of the β-strands taking part in B12 binding in class II are present in class I RNR [39], but not in class III (Figure 6). In line with this, we present a model for how class II and III diverged from the urRNR, and how class I diverged from class II RNR (Figure 9).

Bottom Line: Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms.This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR).While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR).

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden. daniel.lundin@scilifelab.se.

ABSTRACT
Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms. This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR). The mechanism has been deemed unlikely to be catalyzed by a ribozyme, creating an enigma regarding how the building blocks for DNA were synthesized at the transition from RNA- to DNA-encoded genomes. While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR). From the protoRNR evolved the ancestor to modern RNRs, the urRNR, which diversified into the modern three classes. Since the initial radical generation differs between the three modern classes, it is difficult to establish how it was generated in the urRNR. Here we suggest a model that is similar to the B12-dependent mechanism in modern class II RNRs.

No MeSH data available.