Aminoacyl-tRNA synthetases functions

Aminoacyl-tRNA synthetase functions in two steps to bring about the attachment of an amino acid to its cognate tRNA. Does it show specificity for either the amino acid or the tRNA at each of these steps ... 

Cech s group was the first to have success in this direction (Piccirilli, 1992). Using a genetically modified Tetrahymena ribozyme, they were able to hydrolyse an ester bond between the amino acid A-formylmethionine and the corresponding tRNAf Met. The reaction was, however, very slow, only about 5 to 15 times faster than the uncatalysed reaction. The authors ventured to suggest that these ribozymes could have functioned as the first aminoacyl tRNA synthetases. 

The tRNA synthetases may provide a check to make sure that the correct amino acid has been attached to the correct tRNA. If an incorrect amino acid is attached to the tRNA, it will be incorporated into the protein at the position specified by the identity of the tRNA. At least some of the aminoacyl tRNA synthetases have a proofreading function that hydrolyzes any incorrect aminoacyl tRNAs (for example, a Val residue attached to an lie tRNA). 

Among the many proteins that bind to RNA molecules437 39 are the aminoacyl-tRNA synthetases, a variety of other well known enzymes,440 the ribosomal proteins discussed in Chapter 29, and various proteins with dual functions of catalysis and regulation of... 

The aminoacyl-tRNA synthetases join amino acids to their appropriate tRNA molecules for protein synthesis. They have the very important task of selecting both a specific amino acid and a specific tRNA and joining them. The enzymes differ in size and other properties. However, they all appear to function by a common basic chemistry that makes use of cleavage of ATP at Pa (Eq. 12-48) via an intermediate aminoacyl adenylate and that is outlined also in Eq. 17-36. These enzymes are discussed in Chapter 29. ... 

Many proteins have structures related to those of aminoacyl-tRNA synthetases.282 283 For example, asparagine synthetase A functions via an aspartyl-adenylate intermediate (Chapter 24, Section B), and its structure resembls that of aspartyl-tRNA synthetase.284 The his G gene of histidine biosynthesis (Fig. 25-13) encodes an ATP phosphoribosyltransferase with structural homology to the catalytic domain of histidyl-tRNA synthetase.284 The reason is not clear, but some aminoacyl-tRNA synthetases, especially the histidyl-tRNA synthetase, are common autoantigens for the inflammatory disease polymyosititis.285 286... 

Aminoacyl-tRNA synthetases (aaRSs) compose a family of essential enzymes that attach amino acids covalently to tRNA molecules during protein synthesis. Some aaRSs possess a hydrolytic amino acid editing function to ensure the fidelity of protein synthesis. In addition, aminoacylation can occur by indirect pathways that rely on mischarged tRNA intermediates and enzymes other than aaRSs. Throughout evolution, structural and functional divergence of aaRSs has yielded diverse secondary roles. 

Aminoacyl-tRNA synthetases (aaRSs) are critical components of the translation machinery for protein synthesis in every living cell (1). Each aaRS enzyme in this family links a single amino acid covalently to one or more tRNA isoacceptors to form charged tRNAs. Identity elements within the tRNAs serve as molecular determinants or antideterminants that aid in selection by cognate aaRSs (2). Some aaRSs also have an amino acid editing mechanism to clear their mistakes (3). The canonical aaRSs and aaRS-like proteins have functionally diverged to perform many other important roles in the cell (4, 5). Their versatility and adaptability have provided unique opportunities to develop biotechnology tools and to advance medical research. 

Martinis SA, Plateau P, Cavarelli J, Horentz C. Aminoacyl-tRNA synthetases a family of expanding functions. EMBO J. 1999 18 4591-4596. 

Little is known about archaeal aminoacyl-tRNA synthetases, except that the phenylalanyl tRNA synthetases from the archaea Methanosarcina barkeri and S. acidocaldarius resemble their bacterial and eucaryal counterparts in being tetrameric proteins with an aggregate mass of 270 kDda. The archaeal enzymes, however, do not share antigenic determinants with the bacterial and eucaryal enzymes and are functionally restricted to tRNAs of their own lineage [13,14], Thus, they appear to constitute a third class of tRNA charging enzymes, evolutionarily distinct from those of the other domains. 

Most aminoacyl-tRNA synthetases contain editing sites in addition to activation sites. These complementary pairs of sites function as a dcniMe sieve to ensure very high fidelity. In general, the acylation site rejects amino acids that are larger than the correct one because there is insufficient room for them, whereas the hydrolytic site cleaves activated species tlial are smn//er than the correct one. 

Although the accuracy of translation (approximately one error per 104 amino acids incorporated) is lower than those of DNA replication and transcription, it is remarkably higher than one would expect of such a complex process. The principal reasons for the accuracy with which amino acids are incorporated into polypeptides include codon-anticodon base pairing and the mechanism by which amino acids are attached to their cognate tRNAs. The attachment of amino acids to tRNAs, considered the first step in protein synthesis, is catalyzed by a group of enzymes called the aminoacyl-tRNA synthetases. The precision with which these enzymes esterify each specific amino acid to the correct tRNA is now believed to be so important for accurate translation that their functioning has been referred to collectively as the second genetic code. 

Explain the significance of the following statement The functioning of the aminoacyl-tRNA synthetases is referred to as the second genetic code. 

Furthermore, from these findings the idea that the rRNA has a catalytic function in the ribosomal peptide bond formation is supported. It can be assumed that the selection of the individual aminoacyl-tRNA for the A site is mostly attributed to the specificity of the appropriate aminoacyl-tRNA synthetase together with the specific codon-anticodon interactions, whereas the 23 S rRNA participates in catalyzing peptide bond formation but without side-chain specificity for the amino acid esterified to the tRNA s 3 -terminal nucleoside. In comparison with the prerequisites for specificity of peptidases the peptidyltransferase seems to be an old unspecific ribozyme in accordance with its function in evolution as precursor to extant life. 

Because some amino acids are so similar structurally, aminoacyl-tRNA synthetases sometimes make mistakes. These are corrected, however, by the enzymes themselves, which have a proofreading activity that checks the fit In their amino acid-binding pocket. If the wrong amino acid becomes attached to a tRNA, the bound synthetase catalyzes removal of the amino acid from the tRNA. This crucial function helps guarantee that a tRNA delivers the correct amino acid to the protein-synthesizing machinery. The overall error rate for translation In E. coli Is very low, approximately 1 per... 

Transfer RNA (tRNA). The function of /RNA is to transfer activated amino acids to the ribosome for assembly and incorporation into growing polypeptide chains. tRNA is the smallest of the three types of RNA (about 75 nucleotides). A given tRNA is a specific carrier for only 1 of the 20 amino acids. Before the amino acid can be bound to a tRNA, it must be first activated, or energized, by ATP, its own specific enzyme aminoacyl, tRNA synthetase, and Mn2+ ... 

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