期刊
ACTA TROPICA
卷 119, 期 2-3, 页码 151-159出版社
ELSEVIER
DOI: 10.1016/j.actatropica.2011.05.008
关键词
Brugia malayi; Trehalose-6-phosphate phosphatase; Drug target; Antifilarial; Lymphatic filariasis
资金
- University Grants Commission
- Council for Scientific and Industrial Research, New Delhi, India
The pleiotropic functions of disaccharide trehalose in the biology of nematodes and its absence from mammalian cells suggest that its biosynthesis may provide a useful target for developing novel nematicidal drugs. The trehalose-6-phosphate phosphatase (TPP), one of the enzymes of trehalose metabolism has not been characterized so far in nematodes except the free living nematode Caenorhabditis elegans where it's silencing results into lethal outcomes. This prompted us to clone and characterize Brugia malayi TPP in order to discover novel antifilarial drug target. The recombinant protein (Bm-TPP) was purified with apparent homogeneity on a metal ion column and it was found to possess high phosphatase activity with robust specificity for the substrate trehalose-6-phosphate. Bm-TPP was found to be a member of the HAD-like hydrolase super family II based on the conserved motifs required for catalytic reaction. The K-m for substrate trehalose-6-phosphate was around 0.42 mM with pH optimum similar to 7.0 and the enzyme showed an almost absolute requirement for Mg2+ as a metal ion. Bm-TPP was expressed in all the life-stages of B. malayi. In the absence of an effective macrofilaricidal agent and validated antifilarial drug target, Bm-TPP bodes well as a rational drug target against lymphatic filariasis. (C) 2011 Elsevier B.V. All rights reserved.
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