Sandbox Reserved 992: Difference between revisions
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Clinically, β-lactam antibiotics, characterized by their central chemical structure (Fig 1), are utilized to combat bacterial infections by targeting penicillin-binding proteins (PBPs), also known as transpeptidases. PBPs are enzymes that are located in the cell membrane and function in cross-linking to form the peptidoglycan layer. PBPs have a deprotonated serine which executes nucleophilic attack on the carbonyl carbon. The PBP is then covalently attached to one unit of peptidoglycan. The amino group of an alanine on a second unit of peptidoglycan then performs a second nucleophilic attack on the carbonyl carbon, resulting in two covalently cross-linked peptidoglycan units and the regeneration of the catalytic PBP (Fig 2).1 | Clinically, β-lactam antibiotics, characterized by their central chemical structure (Fig 1), are utilized to combat bacterial infections by targeting penicillin-binding proteins (PBPs), also known as transpeptidases. PBPs are enzymes that are located in the cell membrane and function in cross-linking to form the peptidoglycan layer. PBPs have a deprotonated serine which executes nucleophilic attack on the carbonyl carbon. The PBP is then covalently attached to one unit of peptidoglycan. The amino group of an alanine on a second unit of peptidoglycan then performs a second nucleophilic attack on the carbonyl carbon, resulting in two covalently cross-linked peptidoglycan units and the regeneration of the catalytic PBP (Fig 2).1 | ||
[[Image:Peptidoglycan_cross_linking.png|Fig.2 | [[Image:Peptidoglycan_cross_linking.png|thumb|right|Fig.2 Peptidoglycan with PDB Cross-linking Mechanism]] | ||
The β-lactam ring covalently attaches to PBPs, inhibiting them from executing their role in properly synthesizing the cell wall peptidoglycan layer, via nucleophilic attack of the carbonyl carbon (Fig 3). The β-lactam cannot be removed and thus permanently renders the PBP incapable of its catalytic function in cross-linking. Ultimately, this results in death of bacterial cells from osmotic instability or autolysis.2 | The β-lactam ring covalently attaches to PBPs, inhibiting them from executing their role in properly synthesizing the cell wall peptidoglycan layer, via nucleophilic attack of the carbonyl carbon (Fig 3). The β-lactam cannot be removed and thus permanently renders the PBP incapable of its catalytic function in cross-linking. Ultimately, this results in death of bacterial cells from osmotic instability or autolysis.2 | ||