Exploring the role of L209 residue in the active site of NDM-1 a metallo-β-lactamase.

ABSTRACT:

Background

New Delhi Metallo-β-Lactamase (NDM-1) is one of the most recent additions to the β-lactamases family. Since its discovery in 2009, NDM-1 producing Enterobacteriaceae have disseminated globally. With few effective antibiotics against NDM-1 producers, there is an urgent need to design new drug inhibitors through the help of structural and mechanistic information available from mutagenic studies.

Results/conclusions

In our study we focus the attention on the non-catalytic residue Leucine 209 by changing it into a Phenylalanine. The L209F laboratory variant of NDM-1 displays a drastic reduction of catalytic efficiency (due to low kcat values) towards penicillins, cephalosporins and carbapenems. Thermofluor-based assay demonstrated that NDM-1 and L209F are stable to th

SUBMITTER: Marcoccia F 

PROVIDER: S-EPMC5749715 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature