Subtilisin-like proteases in nematodes
ABSTRACT Cleavage by subtilisin-like proteases (subtilases) is an essential step in post-translational processing of proteins found in organisms ranging from yeast to mammals. Our knowledge of the diversity of this protease family in nematodes is aided by the rapid increase in sequence information, especially from the Brugia malayi genome project. Genetic studies of the subtilases in Caenorhabitis elegans give valuable insight into the biological function of these proteases in other nematode species. In this review, we focus on the subtilases in filarial nematodes as well as other parasitic and free-living nematodes in comparison to what is known in C. elegans. Topics to be addressed include expansion and diversity of the subtilase gene family during evolution, enhanced complexity created by alternative RNA splicing, molecular and biochemical characterization of the different subtilases and the challenges of designing subtilase-specific inhibitors for parasitic nematodes.
- SourceAvailable from: Karl-Erich Jaeger
[Show abstract] [Hide abstract]
- "Among them, family S8 of peptidases, also known as " subtilisin-like " or " subtilase " family, harbors the serine endopeptidase subtilisin and related enzymes with a characteristic Asp/His/Ser catalytic triad and represents the second largest family of serine proteases (Siezen and Leunissen 1997; Siezen et al. 2007; Rawlings et al. 2012). Subtilases are found in archaea, bacteria, viruses, fungi, yeast, and higher eukaryotes (Siezen and Leunissen 1997; Bergeron et al. 2000; Antao and Malcata 2005; Poole et al. 2007). The majority of subtilases is secreted but several members are localized intracellularly (Siezen and Leunissen 1997). "
ABSTRACT: The open reading frame PA1242 in the genome of Pseudomonas aeruginosa PAO1 encodes a putative protease belonging to the peptidase S8 family of subtilases. The respective enzyme termed SprP consists of an N-terminal signal peptide and a so-called S8 domain linked by a domain of unknown function (DUF). Presumably, this DUF domain defines a discrete class of Pseudomonas proteins as homologous domains can be identified almost exclusively in proteins of the genus Pseudomonas. The sprP gene was expressed in Escherichia coli and proteolytic activity was demonstrated. A P. aeruginosa ∆sprP mutant was constructed and its gene expression pattern compared to the wild-type strain by genome microarray analysis revealing altered expression levels of 218 genes. Apparently, SprP is involved in regulation of a variety of different cellular processes in P. aeruginosa including pyoverdine synthesis, denitrification, the formation of cell aggregates, and of biofilms.MicrobiologyOpen 02/2014; 3(1). DOI:10.1002/mbo3.150 · 2.21 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: A microcomputer ring in which each node collects data coming from its own cluster of measuring instruments has been implemented at the microcomputer laboratory of the Industrial Automation Department of the University of Brescia. The authors present the architecture of this ring, and discuss in detail both the structure of each node and the scheme of the diagnostic protocol, used to ensure identification of faulty nodes and reinsertion of repaired onesIEEE Transactions on Instrumentation and Measurement 03/1989; DOI:10.1109/19.19994 · 1.79 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Cathepsin-like enzymes have been identified as potential targets for drug or vaccine development in many parasites, as their functions appear to be essential in a variety of important biological processes within the host, such as molting, cuticle remodeling, embryogenesis, feeding and immune evasion. Functional analysis of Caenorhabditis elegans cathepsin L (Ce-cpl-1) and cathepsin Z (Ce-cpz-1) has established that both genes are required for early embryogenesis, with Ce-cpl-1 having a role in regulating in part the processing of yolk proteins. Ce-cpz-1 also has an important role during molting. RNA interference assays have allowed us to verify whether the functions of the orthologous filarial genes in Brugia malayi adult female worms are similar. Treatment of B. malayi adult female worms with Bm-cpl-1, Bm-cpl-5, which belong to group Ia of the filarial cpl gene family, or Bm-cpz-1 dsRNA resulted in decreased numbers of secreted microfilariae in vitro. In addition, analysis of the intrauterine progeny of the Bm-cpl-5 or Bm-cpl Pro dsRNA- and siRNA-treated worms revealed a clear disruption in the process of embryogenesis resulting in structural abnormalities in embryos and a varied differential development of embryonic stages. Our studies suggest that these filarial cathepsin-like cysteine proteases are likely to be functional orthologs of the C. elegans genes. This functional conservation may thus allow for a more thorough investigation of their distinct functions and their development as potential drug targets.PLoS Neglected Tropical Diseases 02/2009; 3(2):e377. DOI:10.1371/journal.pntd.0000377 · 4.45 Impact Factor