Aminoacylation of tRNA 2′‐ or 3′‐hydroxyl by phosphoseryl‐ and pyrrolysyl‐tRNA synthetases

Englert, Markus; Moses, Sarath; Hohn, Michael J.; Ling, Jiqiang; O’Donoghue, Patrick; Söll, Dieter

doi:10.1016/j.febslet.2013.08.037

Cited by 16 publications

(16 citation statements)

References 38 publications

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“…It is noteworthy that the new adjustment of class IIc and IId takes into account the physicochemical character of the cognate amino acids, the aminoacylation site, and correct quaternary structures among the four proposed subclasses ( Table 3 ). PheRS and SepRS are clear functional outsiders from the subclass IId (AlaRS and bacterial GlyRS); the corresponding amino acids are much bigger than Ala and Gly; the aminoacylation sites are different (3′-OH for AlaRS and GlyRS and 2′-OH for Phe and SepRS ( 27 )), and the quaternary structures are also different, most notably between bacterial GlyRS (α 2 β 2 ) and PheRS (αβ) 2 ( Table 3 ). In this way, subclasses IIc and IId encompass much more homogeneous and coherent members, as opposed to the previous subclass IIc, which included a wide variety of aaRSs ( 25 – 27 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recent phylogenetic trees have not commented on the proposed subdivision ( 27 , 55 ). However, a relationship between AlaRS and bacterial GlyRS has even been suggested based on the insertions in the catalytic core and the C-terminal helical domain ( 57 , 58 ).…”

Section: Discussionmentioning

confidence: 99%

“…The eukaryotic GlyRS belongs to the subclass IIa, specific for hydrophobic and small polar amino acids, with similarities with HisRS, ThrRS, ProRS, and SerRS. Bacterial GlyRS, however, belongs to the subclass IIc, together with PheRS, AlaRS, SepRS, and PylRS, the most heterogeneous group of the three subclasses ( 25 – 27 ). However, there are some studies that place AlaRS or bacterial GlyRS within subclass IIa and/or do not consider the existence of two types of GlyRS belonging to different subclasses ( 28 – 32 ).…”

Section: Introductionmentioning

confidence: 99%

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Structural Insights into the Polyphyletic Origins of Glycyl tRNA Synthetases

Valencia-Sánchez

Rodríguez-Hernández

Ferreira

et al. 2016

Journal of Biological Chemistry

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Glycyl tRNA synthetase (GlyRS) provides a unique case among class II aminoacyl tRNA synthetases, with two clearly widespread types of enzymes: a dimeric (α2) species present in some bacteria, archaea, and eukaryotes; and a heterotetrameric form (α2β2) present in most bacteria. Although the differences between both types of GlyRS at the anticodon binding domain level are evident, the extent and implications of the variations in the catalytic domain have not been described, and it is unclear whether the mechanism of amino acid recognition is also dissimilar. Here, we show that the α-subunit of the α2β2 GlyRS from the bacterium Aquifex aeolicus is able to perform the first step of the aminoacylation reaction, which involves the activation of the amino acid with ATP. The crystal structure of the α-subunit in the complex with an analog of glycyl adenylate at 2.8 Å resolution presents a conformational arrangement that properly positions the cognate amino acid. This work shows that glycine is recognized by a subset of different residues in the two types of GlyRS. A structural and sequence analysis of class II catalytic domains shows that bacterial GlyRS is closely related to alanyl tRNA synthetase, which led us to define a new subclassification of these ancient enzymes and to propose an evolutionary path of α2β2 GlyRS, convergent with α2 GlyRS and divergent from AlaRS, thus providing a possible explanation for the puzzling existence of two proteins sharing the same fold and function but not a common ancestor.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structural Insights into the Polyphyletic Origins of Glycyl tRNA Synthetases

Valencia-Sánchez

Rodríguez-Hernández

Ferreira

et al. 2016

Journal of Biological Chemistry

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“…The pathway to Pyl starts with its synthesis from two molecules of Lys. The PylRS is homologous to PheRS but the acylation site is the 3′, typical of the class II enzymes, indicating that PylRS retains the original character of the class II that later developed the atypical function, which is shared by PheRS and SepRS [ 96 , 97 ].…”

Section: Metabolic Pathwaysmentioning

confidence: 99%

Self-Referential Encoding on Modules of Anticodon Pairs—Roots of the Biological Flow System

Guimarães

2017

Life

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The proposal that the genetic code was formed on the basis of (proto)tRNA Dimer-Directed Protein Synthesis is reviewed and updated. The tRNAs paired through the anticodon loops are an indication on the process. Dimers are considered mimics of the ribosomes—structures that hold tRNAs together and facilitate the transferase reaction, and of the translation process—anticodons are at the same time codons for each other. The primitive protein synthesis system gets stabilized when the product peptides are stable and apt to bind the producers therewith establishing a self-stimulating production cycle. The chronology of amino acid encoding starts with Glycine and Serine, indicating the metabolic support of the Glycine-Serine C1-assimilation pathway, which is also consistent with evidence on origins of bioenergetics mechanisms. Since it is not possible to reach for substrates simpler than C1 and compounds in the identified pathway are apt for generating the other central metabolic routes, it is considered that protein synthesis is the beginning and center of a succession of sink-effective mechanisms that drive the formation and evolution of the metabolic flow system. Plasticity and diversification of proteins construct the cellular system following the orientation given by the flow and implementing it. Nucleic acid monomers participate in bioenergetics and the polymers are conservative memory systems for the synthesis of proteins. Protoplasmic fission is the final sink-effective mechanism, part of cell reproduction, guaranteeing that proteins don’t accumulate to saturation, which would trigger inhibition.

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“…Formation of Pyl-tRNA Pyl follows the two step mechanism common to all aaRSs: Pyl is first activated with ATP to form a pyrrolysyl-adenylate (Pyl-AMP) and then transferred to the 3′-hydroxyl group of the tRNA Pyl terminal adenosine [5] .…”

Section: The Pylrs•trnapyl Systemmentioning

confidence: 99%

Pyrrolysyl-tRNA Synthetase, an Aminoacyl-tRNA Synthetase for Genetic Code Expansion

et al. 2016

Self Cite

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Genetic code expansion (GCE) has become a central topic of synthetic biology. GCE relies on engineered aminoacyl-tRNA synthetases (aaRSs) and a cognate tRNA species to allow codon reassignment by co-translational insertion of non-canonical amino acids (ncAAs) into proteins. Introduction of such amino acids increases the chemical diversity of recombinant proteins endowing them with novel properties. Such proteins serve in sophisticated biochemical and biophysical studies both in vitro and in vivo, they may become unique biomaterials or therapeutic agents, and they afford metabolic dependence of genetically modified organisms for biocontainment purposes. In the Methanosarcinaceae the incorporation of the 22nd genetically encoded amino acid, pyrrolysine (Pyl), is facilitated by pyrrolysyl-tRNA synthetase (PylRS) and the cognate UAG-recognizing tRNAPyl. This unique aaRS•tRNA pair functions as an orthogonal translation system (OTS) in most model organisms. The facile directed evolution of the large PylRS active site to accommodate many ncAAs, and the enzyme’s anticodon-blind specific recognition of the cognate tRNAPyl make this system highly amenable for GCE purposes. The remarkable polyspecificity of PylRS has been exploited to incorporate >100 different ncAAs into proteins. Here we review the Pyl-OT system and selected GCE applications to examine the properties of an effective OTS.

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Aminoacylation of tRNA 2′‐ or 3′‐hydroxyl by phosphoseryl‐ and pyrrolysyl‐tRNA synthetases

Cited by 16 publications

References 38 publications

Structural Insights into the Polyphyletic Origins of Glycyl tRNA Synthetases

Structural Insights into the Polyphyletic Origins of Glycyl tRNA Synthetases

Self-Referential Encoding on Modules of Anticodon Pairs—Roots of the Biological Flow System

Pyrrolysyl-tRNA Synthetase, an Aminoacyl-tRNA Synthetase for Genetic Code Expansion

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