Bacterial cell peptide bond formation

Translation takes place by a sequential passing of the mRNA in the 5 ->3 direction, which places the tRNA In the A-site of the ribosome, while a new tRNA is positioned in the P-site. Peptide bond formation is accomplished in this configuration. As many protein chains can be assembled as there are ribosomes on the messenger strand (Fig. 8.3). (There are some 10,000 ribosomes in a bacterial cell.) These polyribosomes (or polysomes) permit the rapid ampli-... 

Figure 22.2 Cross-linking of bacterial cell wall by formation of new peptide bonds.

The site of action in the 3-lactam antibiotics is muramoylpentapeptide carboxypeptidase, an enzyme that is essential for cross-linking of bacterial cell walls. The antibiotic resembles the substrate of this enzyme (a peptide with the C-terminal sequence D-Ala-D-Ala) and is therefore reversibly bound in the active center. This brings the 3-lactam ring into proximity with an essential serine residue of the enzyme. Nucleophilic substitution then results in the formation of a stable covalent bond between the enzyme and the inhibitor, blocking the active center (see p. 96). In dividing bacteria, the loss of activity of the enzyme leads to the formation of unstable cell walls and eventually death. 

Use Against Gram-positive bacteria, rickettsiae, and many viruses, also in veterinary medicine. C. acts on the peptidyltransferase center in bacterial cells by blocking the formation of peptide bonds. 

Fig. 2. Formation of a stable initiation complex between a 70 S ribosome and messenger RNA. In the final complex fMet-tRNAf " is in the correct position for the formation of a peptide bond. IF-1, IF-2, and IF-3 are the protein initiation factors and fMet-tRNAf " is the formyl methionyl tRNA which is used for the initiation of protein synthesis in prokaryotes. The process in animal cells is thought to be substantially the same, the initiation factors being termed IF-Ml, IF-M2, and IF-M3 and the initiator tRNA, Met-tRNAt . The methionine attached to this tRNA species is not normally formylated but can be so modified by enzymes from bacterial cells.

Multiple enz)mies are involved in the synthesis of the bacterial cell wall. The P-lactam antibiotics bind to several of these enzymes, which are collectively called penicillin binding proteins (PBP) and inhibit the cross-linking of the peptidoglycan strands. The most important PBP, transpeptidase, is involved in the final cross-linking step in cell wall s)mthesis. The cross-linking of the bacterial cell wall involves the formation of new peptide bonds between the pentaglycine of one saccharide chain with... 

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