Aminoacyl-tRNA synthetases binding specificity

Fig. 15.6. Some aminoacyl-tRNA synthetase recognition sites on tRNA. Each aminoacyl-tRNA synthetase is specific for one tRNA, which it recognizes by binding the sequences of nucleotides called the recognition sites, shown in blue. In some cases, the anticodon is a recognition site in others, it is not. This is true for human tRNAs as well as those shown here.

The regions of the tRNA molecule teferred to in Chapter 35 (and illustrated in Figure 35-11) now become important. The thymidine-pseudouridine-cyti-dine (T PC) arm is involved in binding of the amino-acyl-tRNA to the ribosomal surface at the site of protein synthesis. The D arm is one of the sites important for the proper recognition of a given tRNA species by its proper aminoacyl-tRNA synthetase. The acceptor arm, located at the 3 -hydroxyl adenosyl terminal, is the site of attachment of the specific amino acid. 

Importance of the Second Genetic Code Some aminoacyl-tRNA synthetases do not recognize and bind the anticodon of their cognate tRNAs but instead use other structural features of the tRNAs to impart binding specificity. The tRNAs for alanine apparently fall into this category. 

At least one aminoacyl-tRNA synthetase exists for each amino acid. The diverse sizes, subunit composition, and sequences of these enzymes vv ere be vildering for many years. Could it be that essentially all synthetases evolved independently The determination of the three-dimensional structures of several synthetases follo ved by more-refined sequence comparisons revealed that different synthetases are, in fact, related. Specifically, synthetases fall into tvv o classes, termed class I and class II, each of vv hich includes enzymes specific for 10 of the 20 amino acids (Table 29.2). Glutaminyl-tRNA synthetase is a representative of class I. The activation domain for class I has a Rossmann fold (Section 16.1.101. Threonyl-tRNA synthetase (see Figure 29.11) is a representative of class II. The activation domain for class II consists largely of P strands. Intriguingly, synthetases from the tvv o classes bind to different faces of the tRNA molecule (Figure 29.14). The CCA arm of tRNA adopts different conformations to accommodate these interactions the arm is in the helical conformation observed for free tRNA (see Figures 29.5 and 29.6) for class II enzymes and in a hairpin conformation for class I enzymes. These two classes also differ in other ways. 

Why did two distinct classes of aminoacyl-tRNA synthetases evolve The observation that the two classes bind to distinct faces of tRNA suggests at least two possibilities. First, recognition sites on both faces of tRNA may have been required to allow the recognition of 20 different tRNAs. Second, it appears possible that, in some cases, a class I enzyme and a class II enzyme can bind to a tRNA molecule simultaneously without colliding with each other. In this way, enzymes from the two classes could work together to modify specific tRNA molecules. 

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. 

The function of the various tRNA molecules is to bind their specific amino acid. This is made possible by members of the aminoacyl-tRNA synthetase family of enzymes. These act as match-makers and are responsible for the accuracy of amino acid selection. They select their amino acid and marry it to its tRNA. First of all, the tRNA must be charged with its specific amino acid in a reaction catalysed by its specific aminoacyl-tRNA synthetase. 

All the steps take place at the active site of the enzyme. Each amino acid has its own aminoacyl-tRNA synthetase. Each synthetase has two specific binding sites, one for the amino acid and one for the tRNA that will carry that amino acid (Eigure 26.11). 

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