Antibiotics that Affect Cell Wall Synthesis
- The Uniformed Services University of the Health Sciences
- Antibiotics that Affect Cell Wall Synthesis
Last Modified: 2016-03-08
- Unique to bacteria
- Not found in animal or plant cells
- The disaccharide has a tetrapeptide side chain
- The peptide side chains are crossed linked together through a pentaglycine bridge between two disaccharide units.
Gram -: May have a capsule, then outer membrane, then small peptidoglycan cell wall, then cytoplasmic membrane
- MurNac- UDP w/ L-ALA--D-Glu--L-LYS--D-ALA--D-ALA
- In Gram - , the pentapeptide is MurNac w/ ALA--GLU--DAP--ALA--ALA
- In gram - bacteria, the DAP of one peptide chain is bound to the fourth D-ALA of another chain
- pyruvyl transferase is the main enzyme involved in this process
- It binds covalently to the active site of the pyruvyl transferase, which prevents the synthesis of UDP-MurNAc from UDP-GlcNAc
- Then two L-Ala are converted to D-Ala (Racemase enzyme catalyzes this rxn)
- Then the two D-Ala amino acids form a dipeptide with the help of Ligase
- Finally, the D-Ala--D-Ala dipeptide is added to L-Lys --now, there are 5 amino acids
- It acts as a competitive inhibitor of both alanine racemase (which converts L-Ala to D-Ala) and ligase (which binds the two D-Ala amino acids together)
- Therefore, D-Cycloserine interferes w/ the production of the pentapeptide side chain.
2. Addition of GlcNAc and flipping of unit across to extracellular space
3 &4. Addition of pentaglycine bridge to L-Lys using ATP energy
5. Transglycosylation - connecting two disaccharide units together
6. Regeneration of GCL-P
- This binding prevents the precursor (disaccharide GlcNAc-MurNAc unit) from binding the the synthase, which would lead to transglycosylation otherwise
A substitution of D-Ala--D-Lac for normal D-Ala--D-Ala in peptidoglycan synthesis occurs. This decreases the affinity of the molecule for glycopeptides and leads to vancomycin resistance.
- They bind transpeptidases (also known as penicillin binding proteins [PBPs]), which are responsible for catalyzing the formation of the peptide bonds btwn the Pentaglycine bridge and D-Ala
Cause cells to lyse due uninhibited cell growth in a cell with structural degradation of cell wall caused by penicillin.
- Gram + bacteria often make these enzymes in large amts after induction by corresponding antibiotic.
- Gene coding is on a transposon, which hops to another strain
PBP is required for entry of antibiotic into bacterial cell.
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