A’-Acetylmuramic acid

Fig. 1.2 A, peptidoglycan of Escherichia coli. , A -acetylmuramic acid , Af-acetylglucosamine. B, repeating unit of peptidoglycan ofE. coli. L-ala, L-alanine D-glu, D-glutamine DAP, diaminopimelic acid D-aia, D-alanine.

A -acetylmuramic acid) residues. These chains are cross-linked via peptide structures. Part of the peptidoglycan of Staphylococcus aureus is shown here. Amino acid abbreviations are given in Chapter 13. 

This shows the involvement of the lactyl group of the A -acetylmuramic acid in linking the peptide with the carbohydrate via an amide teptide bond. The biological activities of the P-lactam antibiotics, e.g. penicillins and cephalosporins (see Box 13.11), stem from an... 

At the Start of the cross-linking process, the peptide chains from the A -acetylmuramic acid residues have a terminal -Lys-o-Ala-o-Ala sequence. The lysine from one chain then becomes bonded to the penultimate d-alanine of another chain through five glycine residues, at the same time displacing the terminal o-alanine. The mechanism involves a serine residue at the active site of the enzyme. This residue is used to convert an amide linkage into an ester, and a reversal of this sequence provides the new peptide bond. 

This enzyme [EC 3.2.1.17], also called muramidase, catalyzes the hydrolysis of the l,4-/3-linkages between N-acetyl-D-glucosamine and A-acetylmuramic acid in pep-tidoglycan heteropolymers of prokaryotic cell walls. Some chitinases [EC 3.2.1.14] also exhibit this activity. See Kinetic Isotope Effect... 

The glycopeptides are inhibitors of cell wall synthesis. They bind to the terminal carboxyl group on the d-alanyl-D-alanine terminus of the A-acetylglucosamine-A-acetylmuramic acid peptide and prevent polymerization of the linear peptidoglycan by peptidoglycan synthase. They are bactericidal in vitro. 

Conversion of UDP-A-acetylmuramic acid to its pen-tapeptide form occurs by the sequential addition of the necessary amino acids. Each step requires ATP and a specific enzyme that ensures the addition of amino acids in the proper sequence, L-alanine is added first, followed by d-glutamic acid, L-lysine (attached by its a-amino group to the y-carboxyl group of the glutamic acid), and finally the... 

GDP-6-deoxy-D- UDP-A acetylgalactosamine UDP-A acetylmuramic acid lyxo-hexosulose... 

---