Ch

HjN COOH valine

FIGURE 14-9 Distinguishing features of similar amino adds.

amino acids tyrosine and phenylalanine [see Figure 14-9a), the opportunity lor forming a strong and energetically favorable hydrogen bond with the hydroxy! moiety of the former but not the latter allows the synthetase for tyrosine (tyrosy] tRNA synthetase) to discriminate effectively against phenylalanine.

It is more challenging to understand the case of isoleucine and valine, ivhich differ hy only a single methylene group (see Figure 14-9b). Valyl tRNA synthetase can sterically exclude isoleucine from its catalytic pocket because isoleucine is larger than valine. In contrast, valine should slip easily into the catalytic pocket of the isoleucy] tRNA synthetase. Although both amino acids will fit into the synthetase amino acid binding site, interactions with the extra methylene group on isoleucine will provide an extra -2 lo -3 kcal/mol of free energy (see Table 3-1). As we described in Chapter 3, even this relatively small difference in free energy will make binding to isoleucine approximately 100-fold more likely than binding to valine, if the two amino acids are present at equal concentrations. Thus, valine would be attached to isoleucine tRNAs approximately 1% of the time, however, this is an unacceptably high rate of error. As we have seen, the actual frequency of misincorporation is <0.1%. How is such high fidelity achieved?

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