Proteolytic enzymes

About: Proteolytic enzymes is a research topic. Over the lifetime, 23096 publications have been published within this topic receiving 835544 citations.

Mechanisms of granule-dependent killing

Abstract: Cytotoxic T lymphocyte and natural killer cell-initiated cell death is one of the primary mechanisms used by higher organisms to eliminate viruses and transformed cells. In this context, target cell death is rapid and efficient and initiated via two main pathways, involving either the ligation of death receptors or through the granule-exocytosis pathway. The granule-exocytosis pathway has attracted much attention over the past 10 years and consequently, a mechanism for granule-dependent killing has become reasonably well established. In the granule-dependent pathway, several proteolytic enzymes called granzymes are delivered to the target cell, promoting the activation of a family of death-inducing proteases called caspases. If caspases are inhibited by viral proteins or are inactivated through mutation, granzyme-mediated proteolysis of other cellular substrates ensures the timely death of infected or transformed cells. Here, we examine the findings that have shaped our current understanding of the mechanics of granule-dependent killing and discuss recent insights that have clarified some long-standing discrepancies in the granzyme literature.

A comparison of the killer character in different yeasts and its classification.

Abstract: The interactions between 20 killer yeasts of various genera and species were examined. Ten distinct groups were recognised with respect to killer activity and 10 distinct groups with respect to resistance to killer action. Using both killing and resistance phenotypes, 13 classes of killer yeast were found. With the exception of Torulopsis glabrata NCYC 388, non-Saccharomyces strains of yeast were not killed by a member of the genus Saccharomyces. The killer character of the 3 killing groups of Saccharomyces identified could be cured by treatment with cycloheximide or incubation at elevated temperature and the effectiveness of these procedures was indicative of the category of killer yeast examined. Killer yeasts not belonging to the genus Saccharomyces could not be cured of their activity. Double-stranded ribonucleic acids were extracted only from Saccharomyces spp. and the molecular weights of the species present were a function of the killer class to which a strain belonged. By an analysis of the effects of proteolytic enzymes, temperature and pH on killer activity and by gel chromatography of crude preparations of killer factors, the toxins of different killer classes were shown to be biochemically distinct. However all toxins had certain properties in common consistent with there being a protein component essential to killer action.

Fibrinolysis in the animal organism.

Abstract: IT is now known that the action of the fibrinolytic substance produced by certain streptococci is due to its properties as an activator for the transformation of a proenzyme present in blood serum and plasma into a proteolytic enzyme acting on the fibrin This activation can also be carried out by treatment with chloroform (for references see Christensen1 and Kaplan2) Considerable confusion concerning the nomenclature for the substances interacting in the fibrinolysis exists ; but it seems most logical to use the proposal of Loomis, George and Ryder3 According to this, the name 'fibrinolysin' is used for the active fibrinolytic enzyme, while the inactive precursor is termed 'profibrinolysin' The activating principle produced by streptococci, and previously termed fibrinolysin, is called 'streptokinase' This nomenclature expresses thus the similarity between the system in question and certain other enzyme systems, for example, the formation of trypsin and thrombin

Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum.

Abstract: Newly replicated Plasmodium falciparum parasites escape from host erythrocytes through a tightly regulated process that is mediated by multiple classes of proteolytic enzymes. However, the identification of specific proteases has been challenging. We describe here a forward chemical genetic screen using a highly focused library of more than 1,200 covalent serine and cysteine protease inhibitors to identify compounds that block host cell rupture by P. falciparum. Using hits from the library screen, we identified the subtilisin-family serine protease PfSU B1 and the cysteine protease dipeptidyl peptidase 3 (DPAP3) as primary regulators of this process. Inhibition of both DPAP3 and PfSUB1 caused a block in proteolytic processing of the serine repeat antigen (SERA) protein SERA5 that correlated with the observed block in rupture. Furthermore, DPAP3 inhibition reduced the levels of mature PfSUB1. These results suggest that two mechanistically distinct proteases function to regulate processing of downstream substrates required for efficient release of parasites from host red blood cells.