Sandbox Reserved 1488: Difference between revisions
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== Structural insights into β-lactam resistance == | == Structural insights into β-lactam resistance <ref>doi: 10.1074/jbc.RA118.006052</ref> == | ||
Penicillins, carbapenems and cephalosporins mimic the D-Ala-D-Ala sequence in the donor substrate and function as suicide inhibitors. Due to the fact that these PBPs have unusually low affinities for β-lactams, the β-lactam acylation rates are negligible compared with bacterial generation times, allowing the pathogens to survive antibiotic treatment. Of greater concern is the observation that prolonged β-lactam therapy can lead to the emergence of highly resistant strains. β-lactam resistance of PBP4 has also been shown to be due to the inefficient formation of the acyl-PBP intermediate. The molecular basis of PBP4 resistance to β-lactams are related to domain movements about the active site and changes in the structures of the active site motifs. However, they depend upon the particular acyl-adduct formed. | Penicillins, carbapenems and cephalosporins mimic the D-Ala-D-Ala sequence in the donor substrate and function as suicide inhibitors. Due to the fact that these PBPs have unusually low affinities for β-lactams, the β-lactam acylation rates are negligible compared with bacterial generation times, allowing the pathogens to survive antibiotic treatment. Of greater concern is the observation that prolonged β-lactam therapy can lead to the emergence of highly resistant strains. β-lactam resistance of PBP4 has also been shown to be due to the inefficient formation of the acyl-PBP intermediate. The molecular basis of PBP4 resistance to β-lactams are related to domain movements about the active site and changes in the structures of the active site motifs. However, they depend upon the particular acyl-adduct formed. | ||
