Molecular Basis of Influence of A501X Mutations in Penicillin-Binding Protein 2 of Neisseria gonorrhoeae Strain 35/02 on Ceftriaxone Resistance.

ABSTRACT: The increase in the resistance of mutant strains of Neisseria gonorrhoeae to the antibiotic ceftriaxone is pronounced in the decrease in the second-order acylation rate constant, k₂/K_S, by penicillin-binding protein 2 (PBP2). These changes can be caused by both the decrease in the acylation rate constant, k₂, and the weakening of the binding affinity, i.e., an increase in the substrate constant, K_S. A501X mutations in PBP2 affect second-order acylation rate constants. The PBP2^A501V variant exhibits a higher k₂/K_S value, whereas for PBP2^A501R and PBP2^A501P variants, these values are lower. We performed molecular dynamic simulations with both classical and QM/MM potentials to model both

SUBMITTER: Krivitskaya AV 

PROVIDER: S-EPMC11312080 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature