Pepstatin, a New Pepsin Inhibitor Produced by Agtinomygetes

Umezawa, Hamao; Aoyagi, Takaaki; Morishima, Hazime; Matsuzaki, M; Hamada, Masa; Takeuchi, Tomio

doi:10.7164/antibiotics.23.259

Cited by 656 publications

(240 citation statements)

References 9 publications

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“…E64d is a membrane permeable inhibitor of cathepsins B, H and L, 25,26 and pepstatin A is an inhibitor of cathepsin D and E. 27,28 As is the case with the other lysosomal marker, Lamp1 (Fig. 1), GFP-LC3 was not colocalized with TMR-Dextran in control cells and treatment with protease inhibitors did not affect the GFP-LC3 distribution pattern ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3

2007

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Section: Resultsmentioning

confidence: 99%

Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3

2007

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“…Substrate (1 mM stock in Me 2 SO) in 100 l of the same buffer was added to give a final concentration of 2 M. Fluorescence from the substrate hydrolysis was measured for 10 min at excitation and emission wavelengths of 330 and 393 nm, respectively. To confirm that cathepsin D (CatD) activity was being measured, worm extract was preincubated for 10 min with a 20 M concentration of the aspartic protease inhibitor, pepstatin A (PA), prior to the addition of the substrate (29).…”

Section: Methodsmentioning

confidence: 99%

A Multienzyme Network Functions in Intestinal Protein Digestion by a Platyhelminth Parasite

Delcroix

Sajid

Caffrey

et al. 2006

Journal of Biological Chemistry

212

205

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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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“…Further, it was reported Correspondence address: K. von der Helm, Pettenkofer Institute, Pettenkoferstr. 9A, D-8000 Miinchen 2,FRG that the viral-encoded proteases of bovine leukemia virus (BLV), murine leukemia virus (MLV) and human T cell leukemia virus (HTLV I) could be inhibited in vitro by pepstatin A [6], an aspartic protease inhibitor [7]. Recent site-specific mutagenesis of Asp-25 proved that the HIV protease has an aspartic proteolytic site [S-lo], and it was demonstrated that pepstatin A but not some other substances known to block aspartic proteases inhibited in vitro the HIV protease [lo-121. In checking whether pepstatin A also inhibited in vivo the HIV gag processing in cell cultures, we found that intracellular gag processing was partially inhibited [lo], and we have now extended these experiments in HIV-infected cultured cells, studying the inhibitory effect of pepstatin A on viral antigen production, on the formation of active reverse transcriptase RT and on the production of infectious HIV.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of HIV replication in cell culture by the specific aspartic protease inhibitor pepstatin A

et al. 1989

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After incubation of H9 cells infected with human immunodeficiency virus (HIV) with pepstatin A at 10−4 M for 2, 4, or 11 days, the culture medium contained significantly less HIV core antigen (p24) than controls without pepstatin A and no or only borderline activity of reverse transcriptase was detected. In addition, after pepstatin A treatment no infectious HIV at 2 or 4 days and only minimal amounts at 11 days were detectable in the culture medium.

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Pepstatin, a New Pepsin Inhibitor Produced by Agtinomygetes

Cited by 656 publications

References 9 publications

Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3

Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3

A Multienzyme Network Functions in Intestinal Protein Digestion by a Platyhelminth Parasite

Inhibition of HIV replication in cell culture by the specific aspartic protease inhibitor pepstatin A

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