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UDP-galactopyranose mutase, a potential drug target against human pathogenic nematode Brugia malayi.
- Source :
-
Pathogens and disease [Pathog Dis] 2016 Aug; Vol. 74 (6). Date of Electronic Publication: 2016 Jul 26. - Publication Year :
- 2016
-
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 ∼51.15 μM and ∼1.27 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 ∼22.68 and ∼23.0 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.<br /> (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Amino Acid Sequence
Animals
Anthelmintics chemistry
Anthelmintics pharmacology
Anthelmintics therapeutic use
Brugia malayi classification
Brugia malayi drug effects
Brugia malayi genetics
Cloning, Molecular
Enzyme Activation drug effects
Enzyme Inhibitors chemistry
Enzyme Inhibitors pharmacology
Enzyme Inhibitors therapeutic use
Filariasis drug therapy
Filariasis parasitology
Gene Expression
Humans
Intramolecular Transferases antagonists & inhibitors
Intramolecular Transferases chemistry
Intramolecular Transferases genetics
Ligands
Models, Molecular
Parasitic Sensitivity Tests
Phylogeny
Protein Conformation
Protein Multimerization
Sequence Analysis, DNA
Brugia malayi enzymology
Intramolecular Transferases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2049-632X
- Volume :
- 74
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Pathogens and disease
- Publication Type :
- Academic Journal
- Accession number :
- 27465638
- Full Text :
- https://doi.org/10.1093/femspd/ftw072