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Chapter 16 : Antibiotic Inhibitors of Bacterial Protein Synthesis

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Antibiotic Inhibitors of Bacterial Protein Synthesis, Page 1 of 2

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Abstract:

This chapter gives an overview of the structure of tRNA to provide a useful outline for understanding how tRNAs serve as interpreters in the translation of mRNA nucleotide sequences into the amino acid sequence of a polypeptide chain. First, methionine is attached to tRNAf Met by the Met-tRNA synthetase. The initiation complex is now ready to initiate the elongation step. Protein synthesis stops when the ribosome reaches one of the three special nonsense codons—UAA, UAG, and UGA. Although the mechanism of protein synthesis is similar in prokaryotes and eukaryotes, prokaryotic ribosomes differ substantially from those in eukaryotes. Studies of protein folding have led to the observation that large protein chains use molecular chaperones to adopt their correct conformation. The puromycin-peptide complex is then released from the ribosome, halting the elongation step.

Citation: Mascaretti O. 2003. Antibiotic Inhibitors of Bacterial Protein Synthesis, p 219-227. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch16
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Figures

Image of Figure 16.1
Figure 16.1

The ribosome, showing the tRNA-mRNA complex between the 30S and 50S ribosomal subunits, and the A and P sites. The growing polypeptide chain extends through the tunnel of the large subunit. Reprinted from T. K. Ritter and X. H. Wong, Angew. Chem. Int. Ed. 40:3508–3533, 2001, with permission from the publisher.

Citation: Mascaretti O. 2003. Antibiotic Inhibitors of Bacterial Protein Synthesis, p 219-227. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch16
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Image of Figure 16.2
Figure 16.2

Aminoacylation of tRNA by aminoacyl-tRNA synthetases. The first step is formation of aminoacyl adenylate, which remains bound to the active site. In the second step, the aminoacyl group is transferred to the tRNA. The mechanism of this step is somewhat different for the two classes of aminoacyl-tRNA synthetases. For class I enzymes, the aminoacyl group is initially transferred to the 2' hydroxyl of the 3'-terminal adenylate residue and then moved to the 3' hydroxyl by a transesterification reaction. For class II enzymes, the aminoacyl group is tranferred directly to the 3' hydroxyl of the terminal adenylate, as shown.

Citation: Mascaretti O. 2003. Antibiotic Inhibitors of Bacterial Protein Synthesis, p 219-227. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch16
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Image of Figure 16.3
Figure 16.3

Chemical structure of fMet-tRNAf Met

Citation: Mascaretti O. 2003. Antibiotic Inhibitors of Bacterial Protein Synthesis, p 219-227. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch16
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Image of Figure 16.4
Figure 16.4

Formation of a peptide bond by an aminoacyl group transfer reaction. The reaction is catalyzed by the peptidyltransferase center and lengthens the peptide chain by one amino acid residue. Note the transfer of the nascent peptide to the tRNA in the A site.

Citation: Mascaretti O. 2003. Antibiotic Inhibitors of Bacterial Protein Synthesis, p 219-227. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch16
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Image of Figure 16.5
Figure 16.5

Reaction catalyzed by PDF and MAP.

Citation: Mascaretti O. 2003. Antibiotic Inhibitors of Bacterial Protein Synthesis, p 219-227. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch16
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Image of Figure 16.6
Figure 16.6

Structural analogy between puromycin and the aminoacyl terminus of tRNA, showing formation of a peptide bond between puromycin at the A site of a ribosome and the nascent peptide bound to the tRNA at the P site. The product of the reaction is bound weakly at the A site and dissociates from the ribosome, terminating protein synthesis and producing an incomplete, inactive peptide.

Citation: Mascaretti O. 2003. Antibiotic Inhibitors of Bacterial Protein Synthesis, p 219-227. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch16
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References

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Tables

Generic image for table
Table 16.1

Two classes of aminoacyl-tRNA synthetases a, b

Citation: Mascaretti O. 2003. Antibiotic Inhibitors of Bacterial Protein Synthesis, p 219-227. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch16
Generic image for table
Table 16.2

Antibiotics and synthetic antibacterial agents that act by inhibition of bacterial protein synthesis

Citation: Mascaretti O. 2003. Antibiotic Inhibitors of Bacterial Protein Synthesis, p 219-227. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch16

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