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Biochemical and biophysical characterization of the OXA-48-like carbapenemase OXA-436

The crystal structure of the class D β-lactamase OXA-436 was solved to a resolution of 1.80 Å. Higher catalytic rates were found at higher temperatures for the clinically important antibiotic imipenem, indicating better adaptation of OXA-436 to its mesophilic host than OXA-48, which is believed to o...

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Detalles Bibliográficos
Autores principales: Lund, Bjarte Aarmo, Thomassen, Ane Molden, Carlsen, Trine Josefine Warg, Leiros, Hanna-Kirsti Schrøder
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411929/
https://www.ncbi.nlm.nih.gov/pubmed/34473108
http://dx.doi.org/10.1107/S2053230X21008645
Descripción
Sumario:The crystal structure of the class D β-lactamase OXA-436 was solved to a resolution of 1.80 Å. Higher catalytic rates were found at higher temperatures for the clinically important antibiotic imipenem, indicating better adaptation of OXA-436 to its mesophilic host than OXA-48, which is believed to originate from an environmental source. Furthermore, based on the most populated conformations during 100 ns molecular-dynamics simulations, it is postulated that the modulation of activity involves conformational shifts of the α3–α4 and β5–β6 loops. While these changes overall do not cause clinically significant shifts in the resistance profile, they show that antibiotic-resistance enzymes exist in a continuum. It is believed that these seemingly neutral differences in the sequence exist on a path leading to significant changes in substrate selectivity.