The Role of Hydrophobic Nodes in the Dynamics of Class A β-Lactamases.

ABSTRACT: Class A β-lactamases are known for being able to rapidly gain broad spectrum catalytic efficiency against most β-lactamase inhibitor combinations as a result of elusively minor point mutations. The evolution in class A β-lactamases occurs through optimisation of their dynamic phenotypes at different timescales. At long-timescales, certain conformations are more catalytically permissive than others while at the short timescales, fine-grained optimisation of free energy barriers can improve efficiency in ligand processing by the active site. Free energy barriers, which define all coordinated movements, depend on the flexibility of the secondary structural elements. The most highly conserved residues in class A β-lactamases are hydrophobic nodes that stabilize the core. To assess how the stab

SUBMITTER: Olehnovics E 

PROVIDER: S-EPMC8490755 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature