Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteases frequently function not only as individual enzymes but also in cascades or networks. A notable evolutionary switch occurred in one such protease network that is involved in protein digestion in the intestine. In vertebrates, this is largely the work of trypsin family serine proteases, whereas in invertebrates, cysteine proteases of the papain family and aspartic proteases assume the role. Utilizing a combination of protease class-specific inhibitors and RNA interference, we deconvoluted such a network of major endopeptidases functioning in invertebrate intestinal protein digestion, using the parasitic helminth, Schistosoma mansoni as an experimental model. We show that initial degradation of host blood proteins is ordered, occasionally redundant, and substrate-specific. Although inhibition of parasite cathepsin D had a greater effect on primary cleavage of hemoglobin, inhibition of cathepsin B predominated in albumin degradation. Nevertheless, in both cases, inhibitor combinations were synergistic. An asparaginyl endopeptidase (legumain) also synergized with cathepsin B and L in protein digestion, either by zymogen activation or facilitating substrate cleavage. This protease network operates optimally in acidic pH compartments either in the gut lumen or in vacuoles of the intestinal lining cells. Defining the role of each of these major enzymes now provides a clearer understanding of the function of a complex protease network that is conserved throughout invertebrate evolution. It also provides insights into which of these proteases are logical targets for development of chemotherapy for schistosomiasis, a major global health problem.
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PMID:A multienzyme network functions in intestinal protein digestion by a platyhelminth parasite. 1702 79

Homalodisca vitripennis Germar 1821 (Hemiptera: Cicadellidae) [Takiya et al. (2006) Ann Entomol Soc Am 99:648-655; syn. H. coagulata (Say)] salivary gland and gut EST libraries were used to isolate cDNA fragments of the gene transcripts encoding for cathepsin L, asparaginyl endopeptidase, cathepsin B, metalloendopeptidase, cathepsin D, multicatalytic endopeptidase, and a sugar-binding C-type lectin. Transcript levels were evaluated in immature and adult H. vitripennis feeding on sunflower (Helianthus annuus) or cowpea (Vigna unguiculata). Northern blot hybridization results showed that expression of most of the transcripts were similar for all developmental stages and feeding on the two diets examined. However, the expression of the transcript for asparaginyl endopeptidase was less expressed in sunflower-fed adult females compared to sunflower-fed immatures. Also, the expression of the C-type lectin transcript was up-regulated in adults compared to immatures when fed on either diet. Documenting both the presence and variation of transcript expression involved in putative digestive proteolysis in this xylem-feeding leafhopper is noteworthy and aids efforts to design specific diet formulations for mass production of hosts and parasitoids to be used as effective biological control measures.
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PMID:Molecular profiling of proteolytic and lectin transcripts in Homalodisca vitripennis (Hemiptera: Auchenorrhyncha: Cicadellidae) feeding on sunflower and cowpea. 1787 31