Structure, activity and thermostability investigations of OXA-163, OXA-181 and OXA-245 using biochemical analysis, crystal structures and differential scanning calorimetry analysis

The first crystal structures of the class D β -lactamases OXA-181 and OXA-245 were determined to 2.05 and 2.20   Å resolution, respectively; in addition, the structure of a new crystal form of OXA-163 was resolved to 2.07   Å resolution. All of these enzymes are OXA-48-like and have been isolated from different clinical Klebsiella pneumoniae strains and also from other human pathogens such as Pseudomonas aeruginosa and Escherichia coli. Here, enzyme kinetics and thermostability studies are presented and the new crystal structures are used to explain the observed variations. OXA-245 had the highest melting point (Tm = 55.8 ° C), as determined by differential scanning calorimetry, compared with OXA-163 (Tm = 49.4 ° C) and OXA-181 (Tm = 52.6 ° C). The differences could be explained by the loss of two salt bridges in OXA-163 and an overall decrease in the polarity of the surface of OXA-181 compared with OXA-245.
Source: Acta Crystallographica Section F - Category: Biochemistry Authors: Tags: antibiotic resistance thermostability enzyme kinetics X-ray crystal structure carbapenemase β -lactamase OXA-181 OXA-163 OXA-245 research communications Source Type: research