Amino acyl tRNA synthetases

ISOLEUCYL-tRNA SYNTHETASE, AMINO-ACYL tRNA SYNTHETASES Isolobal,... 

METHIONYL-tRNA SYNTHETASE METHIONYL-tRNA FORMYLTRANSFERASE METHIONYL-tRNA SYNTHETASE AMINO-ACYL tRNA SYNTHETASES Method of continuous variation,... 

Remarkably, incorporation of fluorinated amino acids into proteins can also be accomplished in vivo. This supposes that the fluorinated amino acid analogs are recognized by the appropriate amino acyl-tRNA synthetase enzyme with efficiency similar to that of the natural amino acid. The proliferase response elicited by a fluorinated analog (a trifluoroisoleucine derivative) of murine interleukin-2 produced in an appropriate Escherichia coli strain was nearly as high as that of the authentic cytokine, indicating folding into an authentic, native structure [84],... 

By observing changes in nucleotides that alter substrate specificity, researchers have identified nucleotide positions that are involved in discrimination by the amino-acyl-tRNA synthetases. These nucleotide positions seem to be concentrated in the amino acid arm and the anticodon arm, including the nucleotides of the anticodon itself, but are also located in other parts of the tRNA molecule. Determination of the crystal structures of aminoacyl-tRNA synthetases complexed with their cognate tRNAs and ATP has added a great deal to our understanding of these interactions (Fig. 27-17). 

XY Yu, JM Hill, G Yu, W Wang, AF Kluge, P Wendler, P Gallant. Synthesis and structure-activity relationships of a series of novel thiazoles as inhibitors of amino-acyl-tRNA synthetases. Boorg Med Chem Lett 9 375-380, 1999. 

The configuration of AMPS, lsO was shown to be (Rp), corresponding to inversion of configuration, by stereospecific phosphorylation, using the adenylate kinase-pyruvate kinase system, and analysis for bridging and nonbridging l80. Similar approaches have been applied to amino acyl-tRNA synthetases, which also catalyze inversion of P of ATP [79]. 

N-(a-AMIN0ACYL)-5 -0-SULFAM0YLADEN0SINES NATURAL PRODUCT BASED INHIBITORS OF AMINO ACYL tRNA SYNTHETASES... 

Suitable N-substituted sulfamoyladenosines (1) inhibit amino acyl tRNA synthetases (aaTRS s) by mimicking the enzyme bound reaction intermediate 2 (Scheme 1)/ Thus the Structure Activity Relationship (SAR) obtained by varying the R group in structure 1 should probe the key interactions for amino acid selectivity in the aaTRS under investigation. 

A -(a-Aminoacyl)-5 -0-Sulfamoyladenosines Natural Product Based Inhibitors of Amino Acyl tRNA Synthetases 288... 

A given amino acid can match more than one kind of codon. However, a given codon can normally match only one amino acid. There are thus 61 codons to match only 20 amino acids. There are also 3 terminal codons that specify a stop signal to protein synthesis. Amino acyl-tRNA synthetase is an enzyme that attaches amino acids to their corresponding transfer RNA. 

Methionine is linked to these two kinds of tRNAs by the same amino-acyl-tRNA synthetase. A specific enzyme then formylates the amino group of methionine that is attached to tRNAf (Figure 29.21). The activated formyl donor in this... 

Amino acyl tRNA synthetases are enzymes that catalyze the covalent joining of an amino acid to its specific tRNA molecule. E. coli has 20 aminoacyl-tRNA synthetases, each of which recognizes one particular amino acid and one or more tRNAs. The two general classes of aminoacyl-tRNA synthetases (I and II) differ in amino acid sequence, the ways in which they bind their cognate tRNAs, and in their quaternary structures. 

INTERNET LINKS Amino Acyl tRNA Synthetase Data Bank... 

Ammo acid -I- tRNA -I- ATP — amino acyl-tRNA -H AMP -I- PPi amino acyl-tRNA synthetase... 

There is a specific amino acyl-tRNA synthetase for each amino acid these enzymes have two specific binding sites, one for the amino acid and the... 

The sequence-dictated three-dimensional conformation of an RNA molecule is essential in the functionality of several RNA types The ribosomic RNAs fold into structures that scaffold the ribosomes, and the tRNAs fold into defined structures that allow their recognition by both amino-acyl tRNA synthetase and ribosomes. In both cases, some nucleotide sequences that remain single stranded are involved in the enzymatic processes performed by the molecules. Thus, the sequence of an RNA dictates its structure and allows it to perform its function. Both are strictly connected. One single mutation in a rRNA or a tRNA may completely change the favored three-dimensional structure of the molecule and totally impair the RNA s function (s). 

Wakasugi K, Schimmel P. Two distinct cytokines released from a human amino-acyl-tRNA synthetase. Science 1999 284 147-151. 

In the second stage, the mRNA joins with the ribosomes to form polysomes (Figure 30-1), which are templates for forming polypeptide chains. But the a-amino acids required for the synthesis are not directly linked onto the polypeptides by the polysomes. The amino acids are first esterified via their carboxyl groups to the 3 ends of tRNA to form amino acyl-tRNA with the aid of amino acyl-tRNA synthetases. A specific tRNA is required for each type of a-amino acid. 

Most secondary pyrimidines are constituents of tRNA. Together with substituted hypoxanthine, adenine, and guanidine derivatives (D 10.4.1) they are of significance for the spatial structure of the different tRNA species and their specific interaction with amino acyl tRNA synthetase and the ribosomes during protein biosynthesis. 

P.R. Schiramel and D. Soil, Amino-acyl tRNA Synthetases, Ann. 

My close friendship with Charles Yanofsky and the times we spent together revealed to me the power of genetics for probing structure-function relationships of enzymes. Consequently, Bill Folk, Maurizio laccarino and I examined mutational alterations affecting amino acyl tRNA synthetases and John Carbon, Charles Hill, Larry Soli, Folk and Moshe Yaniv studied genetically altered tRNA " " the latter investigations proved to be the most productive because they showed that changes in nucleotide sequences of tRNA could affect the specificity of amino acylation and the translation of codons in mRNA. ... 

Yards, M. and Berg, P. (1967) Recognition of tRNA by amino-acyl tRNA synthetases. J. Molec. Biol.26,419 (1969)11. Effect ofsubstrates on the dynamics of tRNA-enzyme interaction. Ibid.42, l. ... 

Amino acids bind to activating enzymes (amino acyl-tRNA synthetases), which recognize both the amino acid and the appropriate tRNA molecule. The first step is reaction between the amino acid and ATP, to form amino acyl AMP, releasing pyrophosphate. The amino acyl AMP then reacts with the -CCA tail of tRNA to form amino acyl-tRNA, releasing AMP... 

The specificity of these enzymes is critically important to the process of translation. Each enzyme recognizes only one amino acid but will bind and react with all the various tRNA species that carry an anticodon for that amino acid. Mistakes are extremely rare. The easiest possible mistake would be the attachment of valine to the tRNA for isoleucine, or vice versa, because of the close similarity between the structures of these two amino acids (see Figure 4.18). However, it is only about once in every 3,000 times that this mistake occurs. Amino acyl-tRNA synthetases have a second active site that checks that the correct amino acid has been attached to the tRNA and, if this is found not to be the case, hydrolyses the newly formed bond, releasing tRNA and the amino acid. 

Recently we had the opportunity to test the activity of thialysine in protein synthesizing systems from either E.coli,rat liver and rabbit reticulocytes,in a study directed to investigate the activity of another lysine analog,selenalysine(22). It was first studied the activation of thialysine by E.coli and rat liver amino-acyl -tRNA synthetases,by assaying either the ATP-PPi... 

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