The Wolbachia endosymbiont of Brugia malayi has an active phosphoglycerate mutase: a candidate target for anti-filarial therapies

被引:25
作者
Foster, Jeremy M. [1 ]
Raverdy, Sylvine [1 ]
Ganatra, Mehul B. [1 ]
Colussi, Paul A. [1 ]
Taron, Christopher H. [1 ]
Carlow, Clotilde K. S. [1 ]
机构
[1] New England Biolabs Inc, Ipswich, MA 01938 USA
关键词
ALKALINE-PHOSPHATASE; TRYPANOSOMA-BRUCEI; MECHANISM; GENE; CATALYSIS;
D O I
10.1007/s00436-008-1287-7
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
090105 [作物生产系统与生态工程]; 100103 [病原生物学];
摘要
Phosphoglycerate mutases (PGM) interconvert 2- and 3-phosphoglycerate in the glycolytic and gluconeogenic pathways. A putative cofactor-independent phosphoglycerate mutase gene (iPGM) was identified in the genome sequence of the Wolbachia endosymbiont from the filarial nematode, Brugia malayi (wBm). Since iPGM has no sequence or structural similarity to the cofactor-dependent phosphoglycerate mutase (dPGM) found in mammals, it may represent an attractive Wolbachia drug target. In the present study, wBm-iPGM cloned and expressed in Escherichia coli was mostly insoluble and inactive. However, the protein was successfully produced in the yeast Kluyveromyces lactis and the purified recombinant wBm-iPGM showed typical PGM activity. Our results provide a foundation for further development of wBm-iPGM as a promising new drug target for novel anti-filarial therapies that selectively target the endosymbiont.
引用
收藏
页码:1047 / 1052
页数:6
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