Participation of the tRNA A76 Hydroxyl Groups throughout Translation

Weinger, Joshua S.; Strobel, Scott A.

doi:10.1021/bi060183n

Cited by 46 publications

(51 citation statements)

References 92 publications

(111 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The spontaneous hydrolysis rate of Tyr-3Ј-dA76 tRNA Phe was Ϸ5-fold slower than those of Tyr-3Ј-A76 tRNA Phe and Tyr-3Ј-F-A76 tRNA Phe (Fig. 7C) probably because of the inductive effects (ϪI) of the electronegative hydroxyl and fluoride groups, which destabilize the aa-tRNA by withdrawing electrons from the ester linkage (22). (31) and LeuRS (32) did not identify catalytic residues.…”

Section: Figmentioning

confidence: 98%

See 1 more Smart Citation

Mechanism of tRNA-dependent editing in translational quality control

Ling¹,

Roy

Ibba

2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Protein synthesis requires the pairing of amino acids with tRNAs catalyzed by the aminoacyl-tRNA synthetases. The synthetases are highly specific, but errors in amino acid selection are occasionally made, opening the door to inaccurate translation of the genetic code. The fidelity of protein synthesis is maintained by the editing activities of synthetases, which remove noncognate amino acids from tRNAs before they are delivered to the ribosome. Although editing has been described in numerous synthetases, the reaction mechanism is unknown. To define the mechanism of editing, phenylalanyl-tRNA synthetase was used to investigate different models for hydrolysis of the noncognate product Tyr-tRNA Phe . Deprotonation of a water molecule by the highly conserved residue ␤His-265, as proposed for threonyl-tRNA synthetase, was excluded because replacement of this and neighboring residues had little effect on editing activity. Model building suggested that, instead of directly catalyzing hydrolysis, the role of the editing site is to discriminate and properly position noncognate substrate for nucleophilic attack by water. In agreement with this model, replacement of certain editing site residues abolished substrate specificity but only reduced the catalytic efficiency of hydrolysis 2-to 10-fold. In contrast, substitution of the 3-OH group of tRNA Phe severely impaired editing and revealed an essential function for this group in hydrolysis. The phenylalanyl-tRNA synthetase editing mechanism is also applicable to threonyl-tRNA synthetase and provides a paradigm for synthetase editing.proofreading ͉ translation ͉ phenylalanine

show abstract

Section: Figmentioning

confidence: 98%

“…9, discussed in ref. 22). In contrast, structural studies of the ThrRS editing site suggested that two water molecules are specifically activated by editing site residues and subsequently hydrolyze the posttransfer editing substrate (18).…”

mentioning

confidence: 99%

Mechanism of tRNA-dependent editing in translational quality control

Ling¹,

Roy

Ibba

2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…However, PheRS proved to be a competitor with EF-Tu for Tyr-tRNA Phe , resulting in the rebinding of the mischarged species at the editing site. Notice that EF-Tu also acts as an isomerase, using a mixture of the 2′(3′)-aminoacyl tRNA isomers as a substrate, and converting them to uniform 3′ complexes (28,29,34). Therefore, the editing site of PheRS has to be in a position to hydrolyze either the 2′-or 3′-OH misacylated tRNA species.…”

Section: Discussionmentioning

confidence: 99%

“…Elongation of the polypeptide chain on the ribosome occurs at a faster rate (by 15-20 s −1 ) than spontaneous acyl migration (29). Not considered as a rate-limiting step in chain elongation, the joint activities of transacylation and hydrolysis should keep the supply of charged tRNA ahead of its transportation to the ribosomal peptidyl transferase center with EF-Tu.…”

Section: Discussionmentioning

confidence: 99%

“…A vast amount of data implies that an aa-tRNA may exist concurrently in two 2′-O and 3′-O-aminoacylated isomers; i.e., the aminoacyl residue, upon forming an ester bond, migrates between the 2′-and 3′-hydroxyls at the 3′-terminal ribose of the tRNAs (26)(27)(28)(29). These findings trace back to results indicative of a solution equilibrium mixture of 2′ and 3′ isomers of ribose esters, including 2′(3′)-O-phenylalanyladenosine and 2′-and 3′-O-anthranoyladenosine (30,31).…”

Section: Quantum Mechanics/molecular Mechanics Simulation and Its Strmentioning

confidence: 99%

See 1 more Smart Citation

Universal pathway for posttransfer editing reactions: Insights from the crystal structure of Tt PheRS with puromycin

Tworowski

Klipcan

Peretz

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

At the amino acid binding and recognition step, phenylalanyltRNA synthetase (PheRS) faces the challenge of discrimination between cognate phenylalanine and closely similar noncognate tyrosine. Resampling of Tyr-tRNA Phe to PheRS increasing the number of correctly charged tRNA molecules has recently been revealed. Thus, the very same editing site of PheRS promotes hydrolysis of misacylated tRNA species, associated both with cis-and trans-editing pathways. Here we report the crystal structure of Thermus thermophilus PheRS (TtPheRS) at 2.6 Å resolution, in complex with phenylalanine and antibiotic puromycin mimicking the A76 of tRNA acylated with tyrosine. Starting from the complex structure and using a hybrid quantum mechanics/molecular mechanics approach, we investigate the pathways of editing reaction catalyzed by TtPheRS. We show that both 2′ and 3′ isomeric esters undergo mutual transformation via the cyclic intermediate orthoester, and the editing site can readily accommodate a model of Tyr-tRNA Phe where deacylation occurs from either the 2′-or 3′-OH. The suggested pathway of the hydrolytic reaction at the editing site of PheRS is of sufficient generality to warrant comparison with other class I and class II aminoacyl-tRNA synthetases.biosynthesis | aminoacyl-tRNA synthetases | tRNA | puromycin | editing

show abstract

Catalytic Modes in Natural Ribozymes

Harris

2008

Wiley Encyclopedia of Chemical Biology

View full text Add to dashboard Cite

In nature, RNA transmits genetic information, and it catalyzes reactions that are universal in biology. The reactions of phosphorus and carbon esters that are catalyzed by natural ribozymes occur with specific geometries and are susceptible to both acid and base catalysis as well as catalysis that involves metal ions. High‐resolution structures of a few ribozymes implicate the involvement of individual nucleotides in performing these catalytic strategies. Detailed biochemical tests of the mechanisms of these ribozymes provide evidence for the involvement of nucleobase functional groups in acid/base catalysis, yet debate continues concerning their precise roles in proton transfer. Complementary structural and biochemical support has been gained for the involvement of specific RNA functional groups in positioning metal ions for catalysis. Still, only a few systems have been probed in sufficient depth to infer mechanistic detail and to achieve a complete chemical description of how ribozyme active sites enact specific catalytic strategies remains a key goal.

show abstract

Participation of the tRNA A76 Hydroxyl Groups throughout Translation

Cited by 46 publications

References 92 publications

Mechanism of tRNA-dependent editing in translational quality control

Mechanism of tRNA-dependent editing in translational quality control

Universal pathway for posttransfer editing reactions: Insights from the crystal structure of Tt PheRS with puromycin

Catalytic Modes in Natural Ribozymes

Contact Info

Product

Resources

About