Peptidoglycan bacterial cell wall, structure

All aspects relating to the bacterial cell wall structure have been reviewed recently. Among the topics covered are the cytoplasmic steps of peptidoglycan synthesis, Lipid II as biosynthetic intermediate and antibacterial target, PBP structure and catalysis, peptidoglycan hydrolytic remodeling, structural... 

FIGURE 23 Typical bacterial cell wall structures (peptidoglycans). 

The peptidoglycan structure of bacterial cell walls. The shaded areas represent points of attachment of this macromolecule to the rest of the cell wall. The amino sugar units are joined end to end to form long, straight chains. The peptides form cross-links when the amino group of a meso-diaminopimelic acid in one chain replaces the terminal alanine in another chain. Source ... 

When grouped on the basis of similarities in their chemical structure, most antibiotics fall into the categories listed in Table 1.17. S-Lactams, which include penicillins and cephalosporins, exhibit a characteristic /i-lactam core ring structure (a four-atom cyclic amide) (Figure 1.14). They induce their bacteriocidal activity by inhibiting the synthesis of peptidoglycan, an essential component of the bacterial cell wall. 

Because peptidoglycans are unique to bacterial cell walls, with no known homologous structures in mammals, the enzymes responsible for their synthesis are ideal targets for antibiotic action. Antibiotics that hit specific bacterial targets are sometimes called magic bullets. Penicillin and its many synthetic analogs have been used to treat bacterial infections since these drugs came into wide application in World War II. 

T Although D-amino acids do not generally occur in proteins, they do serve some special functions in the structure of bacterial cell walls and peptide antibiotics. Bacterial peptidoglycans (see Fig. 20-23) contain both D-alanine and D-glutamate. D-Amino acids arise directly from the l isomers by the action of amino acid racemases, which have pyridoxal phosphate as cofactor (see Fig. 18-6). Amino acid racemization is uniquely important to bacterial metabolism, and enzymes such as... 

The complex structure of bacterial cell walls is discussed in Chapter 8. However, it is appropriate to mention a few bacterial polysaccharides here. The innermost layer of bacterial cell walls is a porous network of a highly crosslinked material known as pepti-doglycan or murein (see Fig. 8-29). The backbone of the peptidoglycan is a P-l,4-linked... 

Another enzyme-activated inhibitor is the streptomyces antibiotic D-cycloserine (oxamycin), an antitubercular drug that resembles D-alanine in structure. A potent inhibitor of alanine racemase, it also inhibits die non-PLP, ATP-dependent, D-alanyl-D-alanine synthetase which is needed in the biosynthesis of die peptidoglycan of bacterial cell walls. 

Prior to the crystallization of jack bean urease it was assumed by the biochemical community that enzymes had no ordered structure. In 1965 the first crystallographic evidence for the mechanism by which enzymes work when Phillips and his group solved the lysozyme structure [6], Details of the structure indicated how the enzyme could bind the oligosaccharides present in its target, bacterial cell wall peptidoglycans, and could respond to the binding event by changing its structure. 

Fig. 8. Basic structural unit of a peptidoglycan of the bacterial cell wall of Staphylococcus aureus...

The isolation of bacterial DNA described in this experiment, patterned after the work of Marmur (1961), accomplishes these objectives. Bacterial cells are disrupted by initial treatment with the enzyme, egg-white lysozyme, which hydrolyzes the peptidoglycan that makes up the structural skeleton of the bacterial cell wall. The resultant cell walls are unable to withstand osmotic shock. Thus, the bacteria lyse in the hypotonic environment. The detergent, sodium dodecyl sulfate, (SDS, sodium do-decyl sulfate) then completes lysis by disrupting residual bacterial membranes. SDS also reduces harmful enzymatic activities (nucleases) by its ability to denature proteins. The chelating agents, citrate and EDTA (ethylenediamine tetraacetic acid), also inhibit nucleases by removing divalent cations required for nuclease activity. 

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