BIOCHEMISTRY - L. Stryer - 1984

VOLUME 3

PART V. MOLECULAR PHYSIOLOGY

CHAPTER 32. BACTERIAL CELL WALLS

32.5. Synthesis of the Disaccharide-Peptide Unit Attached to a Lipid Carrier

The next step is The addition of NAG to the NAM residue within the carbohydrate-peptide unit attached to the lipid carrier. The activated carbohydrate donor, UDP-NAG, reacts with the C-4 position of the NAM residue, forming a β-1,4-glycosidic linkage between these sugars (Fig. 32.9). Subsequently, in an ATP-dependent reaction, NH4+ amidates the free α-carboxyl group of D-glutamic acid in the peptide. Following this, a pentaglycine bridge is assembled on the ε-amino group of the Lysine residue within the peptide.

Class="center">Fig. 32.9. Synthesis of the disaccharide-peptide unit on the lipid carrier

This pentapeptide is synthesized through the sequential addition of Glycine residues delivered by glycyl-tRNA. This is the sole instance where tRNA serves as an amino acid donor during nonribosomal Peptide Synthesis. This completes The formation of the primary structural unit of The Cell wall.

32.6. Transfer of the Disaccharide-Peptide Unit to the Growing Polysaccharide Chain

The disaccharide-peptide unit is transferred by the lipid carrier to the nonreducing end of the growing polysaccharide chain. The reaction proceeds as follows. The C-1 carbon atom of the NAM residue is in an activated state because it is linked to the lipid carrier by a pyrophosphate bond. Consequently, it reacts with the C-4 hydroxyl of the terminal NAG residue of the growing polysaccharide chain, thereby forming a β-1,4-glycosidic bond (Fig. 32.10).

Fig. 32.10. Transfer of the disaccharide-peptide unit to the growing polysaccharide chain

The lipid carrier is released as pyrophosphate and subsequently hydrolyzed to monophosphate by a specific phosphatase. This dephosphorylation step essentially regenerates the carrier, enabling it to accept another carbohydrate-peptide unit from UDP. The peptide antibiotic bacitracin is known to inhibit cell wall Biosynthesis by blocking this specific step:

32.7. Cross-Links Between Polysaccharide Chains Are Formed via Transpeptidation

As a result of the transpeptidation reaction, cross-links are formed between the polysaccharide chains, leading to the creation of a single giant, sac-like molecule. During transpeptidation, the terminal amino group of one pentaglycine bridge attacks the peptide bond between the D-Ala-D-Ala residues of another peptide unit (Fig. 32.11). This forms a peptide bond between glycine and one of the D-Alanine residues, while the second D-alanine residue is released. The enzyme catalyzing this reaction is glycopeptide transpeptidase. Note that the synthesis of this cross-link does not require the expenditure of ATP; the reaction is driven by the Free energy already contained within the D-Ala-D-Ala bond. The Formation of the peptide bond in this unusual manner is clearly dictated by the fact that the reaction takes place outside The Cell, i.e., in the absence of ATP. Recall that peptide bonds during the cross-linking of fibrin strands are also formed via Transamination without the utilization of ATP (Section 8.21).

Fig. 32.11. The amino group of the pentaglycine bridge attacks the peptide bond between two D-Ala residues, resulting in the formation of a cross-link

32.8. In Gram-Positive Bacteria, Peptidoglycan Is Coated with Teichoic Acid

The surface of Gram-positive Bacteria consists of teichoic acid, which is a polymer of glycerol residues (or another carbohydrate, such as ribitol) connected by phosphodiester bridges (Fig. 32.12). Free hydroxyl groups are esterified with alanine or sugars, notably glucose. Teichoic acid is attached to the peptidoglycan backbone—The sequence of NAG-NAM residues—via a phosphodiester bond. Elongation of the teichoic acid chains occurs through The transfer of glycerol phosphate from CDP-glycerol to the free terminal OH group of the chain. Glucose residues are attached to the hydroxyl groups of the teichoic acid backbone via a reaction with UDP-glucose.

Fig. 32.12. Structure of teichoic acid