High adaptability of the omega loop underlies the substrate-spectrum-extension evolution of a class A β-lactamase, PenL.

ABSTRACT: The omega loop in β-lactamases plays a pivotal role in substrate recognition and catalysis, and some mutations in this loop affect the adaptability of the enzymes to new antibiotics. Various mutations, including substitutions, deletions, and intragenic duplications resulting in tandem repeats (TRs), have been associated with β-lactamase substrate spectrum extension. TRs are unique among the mutations as they cause severe structural perturbations in the enzymes. We explored the process by which TRs are accommodated in order to test the adaptability of the omega loop. Structures of the mutant enzymes showed that the extra amino acid residues in the omega loop were freed outward from the enzyme, thereby maintaining the overall enzyme integrity. This structural adjustment was accompanied by di

SUBMITTER: Yi H 

PROVIDER: S-EPMC5101513 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature