Molecular dynamics of class A β-lactamases-effects of substrate binding.

ABSTRACT: The effects of substrate binding on class A β-lactamase dynamics were studied using molecular dynamics simulations of two model enzymes; 40 100-ns trajectories of the free and substrate-bound forms of TEM-1 (with benzylpenicillin) and PSE-4 (with carbenicillin) were recorded (totaling 4.0 μs). Substrates were parameterized with the CHARMM General Force Field. In both enzymes, the Ω loop exhibits a marked flexibility increase upon substrate binding, supporting the hypothesis of substrate gating. However, specific interactions that are formed or broken in the Ω loop upon binding differ between the two enzymes: dynamics are conserved, but not specific interactions. Substrate binding also has a global structuring effect on TEM-1, but not on PSE-4. Changes in TEM-1's normal modes show long-rang

SUBMITTER: Fisette O 

PROVIDER: S-EPMC3475387 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature