UDP-galactopyranose mutase, a potential drug target against human pathogenic nematode Brugia malayi.
Pathog Dis
; 74(6)2016 08.
Article
en En
| MEDLINE
| ID: mdl-27465638
ABSTRACT
Lymphatic filariasis, a vector-borne neglected tropical disease affects millions of population in tropical and subtropical countries. Vaccine unavailability and emerging drug resistance against standard antifilarial drugs necessitate search of novel drug targets for developing alternate drugs. Recently, UDP-galactopyranose mutases (UGM) have emerged as a promising drug target playing an important role in parasite virulence and survival. This study deals with the cloning and characterization of Brugia malayi UGM and further exploring its antifilarial drug target potential. The recombinant protein was actively involved in conversion of UDP-galactopyranose (substrate) to UDP-galactofuranose (product) revealing Km and Vmax to be â¼51.15 µM and â¼1.27 µM/min, respectively. The purified protein appeared to be decameric in native state and its 3D homology modeling using Aspergillus fumigatus UGM enzyme as template revealed conservation of active site residues. Two specific prokaryotic inhibitors (compounds A and B) of the enzyme inhibited B. malayi UGM enzymatic activity competitively depicting Ki values â¼22.68 and â¼23.0 µM, respectively. These compounds were also active in vitro and in vivo against B. malayi The findings suggest that B. malayi UGM could be a potential antifilarial therapeutic drug target.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Brugia Malayi
/
Transferasas Intramoleculares
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Pathog Dis
Año:
2016
Tipo del documento:
Article
País de afiliación:
India