Search results for "Protease"
showing 10 items of 463 documents
Ultrastructural evidence of collagenolytic activity in ductal infiltrating carcinoma of the human breast
1987
The stroma of ductal infiltrating carcinoma of the human breast shows characteristic and localized areas of collagen rarefaction and fragmentation. This finding has been correlated with a peculiar type of fibrillar damage, observed in a small percentage of collagen fibrils isolated in the native state from the tumour stroma. The same pattern of lesion has been reproduced in vitro by human collagenase digestion on reconstituted fibrils. No effect has been detected by other nonspecific proteases in the same system.
Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia
2013
Author version made available in accordance with the publisher's policy.
Tetanus Toxin Inhibits Neuroexocytosis Even When Its Zn2+-dependent Protease Activity Is Removed
1995
Tetanus toxin (TeTX) is a dichain protein that blocks neuroexocytosis, an action attributed previously to Zn(2+)-dependent proteolysis of synaptobrevin (Sbr) by its light chain (LC). Herein, its cleavage of Sbr in rat cerebrocortical synaptosomes was shown to be minimized by captopril, an inhibitor of certain metalloendoproteases, whereas this agent only marginally antagonized the inhibition of noradrenaline release, implicating a second action of the toxin. This hypothesis was proven by preparing three mutants (H233A, E234A, H237A) of the LC lacking the ability to cleave Sbr and reconstituting them with native heavy chain. The resultant dichains were found to block synaptosomal transmitter…
Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line.
1999
An estimated 170 million persons worldwide are infected with hepatitis C virus (HCV), a major cause of chronic liver disease. Despite increasing knowledge of genome structure and individual viral proteins, studies on virus replication and pathogenesis have been hampered by the lack of reliable and efficient cell culture systems. A full-length consensus genome was cloned from viral RNA isolated from an infected human liver and used to construct subgenomic selectable replicons. Upon transfection into a human hepatoma cell line, these RNAs were found to replicate to high levels, permitting metabolic radiolabeling of viral RNA and proteins. This work defines the structure of HCV replicons funct…
Fetuin-A and Cystatin C Are Endogenous Inhibitors of Human Meprin Metalloproteases
2010
Meprin α and β, zinc metalloproteinases, play significant roles in inflammation, including inflammatory bowel disease (IBD), possibly by activating cytokines, like interleukin 1β, interleukin 18, or tumor growth factor α. Although a number of potential activators for meprins are known, no endogenous inhibitors have been identified. In this work, we analyzed the inhibitory potential of human plasma and identified bovine fetuin-A as an endogenous meprin inhibitor with a K(i) (inhibition constant) of 4.2 × 10(-5) M for meprin α and a K(i) of 1.1 × 10(-6) M meprin β. This correlated with data obtained for a fetuin-A homologue from carp (nephrosin inhibitor) that revealed a potent meprin α and β…
Kathepsinaktivit�t im menschlichen Endometrium
1955
Die nach der Methode vonAnson bestimmte Kathepsinaktivitat im menschlichen Endometrium wahrend der verschiedenen Cyclusphasen zeigte keine signifikanten Unterschiede.
Synthesis and activity of phosphinic tripeptide inhibitors of cathepsin C
2004
Phosphinic tripeptide analogues Gly-Xaaψ[P(O)(OH)CH2]-Gly have been developed as inhibitors of cathepsin C (DPP I), a lysosomal, papain-like cysteine protease. The target compounds were synthesised by addition of methyl acrylate to the appropriate phosphinic acids followed by the N-terminus elongation using mixed anhydride procedure. The latter step has been demonstrated to be a suitable method for N-terminal extension of the phosphinic pseudopeptide analogues without requirement of hydroxyphosphinyl protection. The title compounds appeared to be moderate inhibitors of the cathepsin C. However, although designed as transition state analogues, they surprisingly exhibited noncompetitive mode …
Characterization of fusion from without induced by herpes simplex virus
1991
The process of fusion from without (FFWO) induced by herpes simplex virus (HSV) was analyzed by using various inhibitors and compared to fusion from within (FFWI). The fate of certain elements of the cytoskeleton after FFWO was also investigated. Our experiments demonstrate FFWO as a very suitable system for study of early virus-cell interactions. Zn++ ions proved inhibitory for penetration whilst pretreatment of cells with Ca++ ions before infection enhanced FFWO activity. Dissociation of penetration from the fusion process itself was possible by use of Zn++ ions, low pH-treatment and antiserum on the one hand and N-ethylmaleimide and cytochalasin D on the other. Penetration itself needs o…
Autocatalytic cleavage of Clostridium difficile toxin B.
2007
Clostridium difficile, the causative agent of nosocomial antibiotic-associated diarrhoea and pseudomembranous colitis, possesses two main virulence factors: the large clostridial cytotoxins A and B. It has been proposed that toxin B is cleaved by a cytosolic factor of the eukaryotic target cell during its cellular uptake. Here we report that cleavage of not only toxin B, but also all other large clostridial cytotoxins, is an autocatalytic process dependent on host cytosolic inositolphosphate cofactors. A covalent inhibitor of aspartate proteases, 1,2-epoxy-3-(p-nitrophenoxy)propane, completely blocked toxin B function on cultured cells and was used to identify its catalytically active prote…
Ensemble-based ADME-Tox profiling and virtual screening for the discovery of new inhibitors of the Leishmania mexicana cysteine protease CPB2.8ΔCTE
2018
Abstract: In an effort to identify novel molecular warheads able to inhibit Leishmania mexicana cysteine protease CPB2.8CTE, fused benzo[b]thiophenes and ,'-triketones emerged as covalent inhibitors binding the active site cysteine residue. Enzymatic screening showed a moderate-to-excellent activity (12%-90% inhibition of the target enzyme at 20m). The most promising compounds were selected for further profiling including in vitro cell-based assays and docking studies. Computational data suggest that benzo[b]thiophenes act immediately as non-covalent inhibitors and then as irreversible covalent inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3'-triketones with a Y-to…