Furthermore, we explore temocillin's mechanism of β-lactamase inhibition with a high-resolution complex structure of CTX-M-14 class A serine β-lactamase. This hypothesis is supported by the observation that the acyl-enzyme complex of temocillin has reduced thermal stability compared with ticarcillin. Most notably, the 6-α-methoxy group disrupts a high-quality hydrogen bond with a conserved residue important for ligand binding while also being inserted into a crowded active site, possibly destabilizing the active site and enabling water molecule from bulk solvent to access and cleave the acyl-enzyme bond. Complex crystal structures with PBP3 reveal similar binding modes of the two drugs but with important differences. aeruginosa We show that the 6-α-methoxy group perturbs the stability of the PBP3 acyl-enzyme, which manifests in an elevated off-rate constant ( k off ) in biochemical assays comparing temocillin with ticarcillin.
We review here responses of the bacterium P. aeruginosa to antimicrobials is therefore important. This organism can be exposed to a wide range of concentrations of antimicrobials during treatment learning more about the responses of P. Here, we analyze the reaction kinetics, protein stability, and binding conformations of temocillin and ticarcillin with penicillin-binding protein 3 (PBP3), an essential PBP in P. Infections caused by Pseudomonas aeruginosa often are hard to treat inappropriate chemotherapy readily selects multidrug-resistant P. Similarly, our results show also that PBP3 has the highest affinity for imipenem in H. aeruginosa have remained relatively unexplored. These observations strongly suggest that an altered PBP3 protein is linked to imipenem heteroresistance. The origins of temocillin's inferior antibacterial properties against P. The α-methoxy modification confers resistance to serine β-lactamases, yet temocillin is ineffective against P. Temocillin is the 6-α-methoxy analogue of ticarcillin, a carboxypenicillin with well-characterized antipseudomonal properties. One was the / domain, which was covered by two helices (1 in N-terminal and 10 in C-terminal) on one side of a seven parallel sheets (1-7), with the other side covered by 3 and 8 helix. licheniformis ATCC14580 was shown in Fig. The 3D structure of BlaR-CTD protein from B. The prevalence of multidrug-resistant Pseudomonas aeruginosa has led to the reexamination of older "forgotten" drugs, such as temocillin, for their ability to combat resistant microbes. Homologous model of BlaR-CTD and docking with -lactams.
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