Limits...
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.


Structure of the monomeric class II RNR from L. leichmannii (PDB: 1L1L [39]). Helices A and B are yellow and the dimer-mimicking insertion is pink.
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life-05-00604-f011: Structure of the monomeric class II RNR from L. leichmannii (PDB: 1L1L [39]). Helices A and B are yellow and the dimer-mimicking insertion is pink.

Mentions: Although class II RNR in many respects appears ancient in comparison with the arguably more sophisticated two component systems with stable protein radicals—class I and III—class II showcases one of the most spectacular evolutionary inventions in RNR posterior to the urRNR and allosteric regulation: The insertion of a dimer-mimicking domain [39], defining a monophyletic subclass encoded by bacterial genomes and a few unicellular Eukaryotes due to horizontal gene transfer [66]. The normal dimer-dependent allosteric substrate specificity mechanism of RNRs closely aligns with models for oligomer-dependent allostery proposed in the mid-1960s [94,95]. Conversely, the monomeric class II RNR is independent of quaternary structure as the effector binds in a pocket formed by helices in a 130 amino acid insertion in the sequence (Figure 11). There are other examples of monomeric enzymes exhibiting allosteric regulation [96,97], but what makes monomeric class II RNR unique is that it evolved from a dimer. It presumably conserves the mechanism from the dimeric enzyme, as suggested by the structural similarity between the dimer interface of class I/II RNR and the pocket formed by the insertion.


The origin and evolution of ribonucleotide reduction.

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

Structure of the monomeric class II RNR from L. leichmannii (PDB: 1L1L [39]). Helices A and B are yellow and the dimer-mimicking insertion is pink.
© Copyright Policy
Related In: Results  -  Collection

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

life-05-00604-f011: Structure of the monomeric class II RNR from L. leichmannii (PDB: 1L1L [39]). Helices A and B are yellow and the dimer-mimicking insertion is pink.
Mentions: Although class II RNR in many respects appears ancient in comparison with the arguably more sophisticated two component systems with stable protein radicals—class I and III—class II showcases one of the most spectacular evolutionary inventions in RNR posterior to the urRNR and allosteric regulation: The insertion of a dimer-mimicking domain [39], defining a monophyletic subclass encoded by bacterial genomes and a few unicellular Eukaryotes due to horizontal gene transfer [66]. The normal dimer-dependent allosteric substrate specificity mechanism of RNRs closely aligns with models for oligomer-dependent allostery proposed in the mid-1960s [94,95]. Conversely, the monomeric class II RNR is independent of quaternary structure as the effector binds in a pocket formed by helices in a 130 amino acid insertion in the sequence (Figure 11). There are other examples of monomeric enzymes exhibiting allosteric regulation [96,97], but what makes monomeric class II RNR unique is that it evolved from a dimer. It presumably conserves the mechanism from the dimeric enzyme, as suggested by the structural similarity between the dimer interface of class I/II RNR and the pocket formed by the insertion.

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.