Analysis of a novel class A β-lactamase OKP-B-6 of Klebsiella quasipneumoniae: structural characterisation and interaction with commercially available drugs
Título del documento: Analysis of a novel class A β-lactamase OKP-B-6 of Klebsiella quasipneumoniae: structural characterisation and interaction with commercially available drugs
Revista: Memorias do Instituto Oswaldo Cruz
Base de datos: PERIÓDICA
Número de sistema: 000452389
ISSN: 0074-0276
Autores: 1
1
1
1
1
1
Instituciones: 1Laboratorio Nacional de Computacao Cientifica, Petropolis, Rio de Janeiro. Brasil
Año:
Volumen: 117
País: Brasil
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Analítico, descriptivo
Resumen en inglés Gram-negative and Gram-positive bacteria produce beta-lactamase as factors to overcome beta-lactam antibiotics, causing their hydrolysis and impaired antimicrobial action. Class A beta-lactamase contains the chromosomal sulfhydryl reagent variable (SHV, point mutation variants of SHV-1), LEN (Klebsiella pneumoniae strain LEN-1), and other K. pneumoniae beta-lactamase (OKP) found mostly in Klebsiella’s phylogroups. The SHV known as extended-spectrum β-lactamase can inactivate most beta-lactam antibiotics. Class A also includes the worrisome plasmid-encoded Klebsiella pneumoniae carbapenemase (KPC-2), a carbapenemase that can inactivate most beta-lactam antibiotics, carbapenems, and some beta-lactamase inhibitors. OBJECTIVES So far, there is no 3D crystal structure for OKP-B, so our goal was to perform structural characterisation and molecular docking studies of this new enzyme. METHODS We applied a homology modelling method to build the OKP-B-6 structure, which was compared with SHV-1 and KPC-2 according to their electrostatic potentials at the active site. Using the DockThor-VS, we performed molecular docking of the SHV-1 inhibitors commercially available as sulbactam, tazobactam, and avibactam against the constructed model of OKP-B-6. FINDINGS From the point of view of enzyme inhibition, our results indicate that OKP-B-6 should be an extended-spectrum beta-lactamase (ESBL) susceptible to the same drugs as SHV-1. MAIN CONCLUSIONS This conclusion advantageously impacts the clinical control of the bacterial pathogens encoding OKP-B in their genome by using any effective, broad-spectrum, and multitarget inhibitor against SHV-containing bacteria
Disciplinas: Medicina
Palabras clave: Farmacología,
Bacterias,
Diseño de fármacos,
Beta-lactamasa,
Acoplamiento molecular,
Klebsiella quasipneumoniae
Keyword: Pharmacology,
Bacteria,
Drug design,
Beta-lactamase,
Molecular docking,
Klebsiella quasipneumoniae
Texto completo: Texto completo (Ver HTML) Texto completo (Ver PDF)