Search results for "Endopeptidase"
showing 10 items of 361 documents
Candidate Targets for Hepatitis C Virus-Specific Antiviral Therapy
1997
The hepatitis C virus (HCV) was identified as the major causative agent of posttransfusion and community-acquired non-A, non-B hepatitis throughout the world. It is an enveloped virus with a plus-strand RNA genome encoding a polyprotein of about 3,010 amino acids. This polyprotein is cleaved co- and posttranslationally into mature viral proteins by host cell signal peptidases and 2 viral enzymes designated the NS2-3 proteinase and the NS3/4A proteinase complex. It is assumed that virus replication takes place in a membrane-associated complex containing at least 2 viral enzymatic activities: the NS3 nucleoside triphosphatase (NTPase)/helicase and the NS5B RNA-dependent RNA polymerase (RdRp).…
Caspase-mediated apoptosis in sponges: cloning and function of the phylogenetic oldest apoptotic proteases from Metazoa
2003
AbstractSponges (phylum Porifera) represent the phylogenetically oldest metazoan phylum. These animals have complex cell adhesion and powerful immune systems which allow the formation of a distinct body plan. Consequently, an apoptotic machinery has to be predicted that allows sponges to eliminate unwanted cells accumulating during development. With the marine sponge Geodia cydonium, it is shown that allografts of these animals undergo apoptosis as demonstrated by apoptotic DNA fragmentation. Extracts from allografts contain an enzymic activity characteristic for caspases; as substrate to determine the cleavage activity, Ac-DEVD-AMC was applied. cDNAs encoding predicted caspase-3-related pr…
Two α subunits and one β subunit of meprin zinc-endopeptidases are differentially expressed in the zebrafish Danio rerio
2007
Abstract Meprins are members of the astacin family of metalloproteases expressed in epithelial tissues, intestinal leukocytes and certain cancer cells. In mammals, there are two homologous subunits, which form complex glycosylated disulfide-bonded homo- and heterooligomers. Both human meprin α and meprin β cleave several basement membrane components, suggesting a role in epithelial differentiation and cell migration. There is also evidence that meprin β is involved in immune defence owing to its capability of activating interleukin-1β and the diminished mobility of intestinal leukocytes in meprin β-knockout mice. Here we show for the first time by reverse transcription PCR, immunoblotting a…
Cloning and characterization of PRB1, a Candida albicans gene encoding a putative novel endoprotease B and factors affecting its expression
2002
Abstract Several cDNA fragments corresponding to transcripts differentially expressed under conditions that favor mycelial growth of Candida albicans were identified by the “differential display” technique. One of these was cloned and used as a probe to rescue the full gene from a genomic library of the fungus. The sequence identified a single, uninterrupted open reading frame of 1395 nucleotides encoding a putative protein of 465 residues and a theoretical molecular weight of 50.3 kDa, present in the genome as a single copy located at chromosome 2 in different strains. The gene product showed high homology with subtilisin-like proteases, mainly PRB1, the vacuolar B protease from Saccharomy…
Machine Learning Unveils Proteotypic Mimicry in Genetically Defined SCN Variants
2019
Background Novel computational algorithms for multi-omics analysis bear great potential to highlight pathomechanisms of monogenic diseases. We recently defined the in-depth proteome of primary human neutrophil granulocytes (PMID 30630937). Here, we ask the question whether proteotypic patterns differ between defined genetic subtypes associated with severe congenital neutropenia (SCN). We focus on two novel genetic variants in constituents of the signal recognition particle (SRPRA and SRP19) and previously reported SCN genotypes SRP54, HAX1, and ELANE. Methods We analyzed proteomes of highly purified neutrophil granulocytes from a total of 26 SCN patients, including 5 with homozygous splice …
Leucine Aminopeptidase Activity in Mast Cells
1959
DURING investigations of the behaviour of leucine aminopeptidase activity of blood-serum in patients with dermatoses and tumours1–3, in a case of diffuse skin mastocytosis of a new-born, we detected heightened activity of leucine aminopeptidase. After mechanical friction of the affected skin, greater activity of leucine aminopeptidase occurred. From this we supposed a release of leucine aminopeptidase from the mast cell infiltrates of the skin. As is well known, in urticaria pigmentosa mechanical irritation of the skin lesions give rise to a degranulation of mast cells4,5 with liberation of histamine and serotonin. Indeed, there is no doubt that mast cells contain the enzyme leucine aminope…
The crystal structure of a 250-kDa heterotetrameric particle explains inhibition of sheddase meprin β by endogenous fetuin-B
2021
Meprin β (Mβ) is a multidomain type-I membrane metallopeptidase that sheds membrane-anchored substrates, releasing their soluble forms. Fetuin-B (FB) is its only known endogenous protein inhibitor. Herein, we analyzed the interaction between the ectodomain of Mβ (MβΔC) and FB, which stabilizes the enzyme and inhibits it with subnanomolar affinity. The MβΔC:FB crystal structure reveals a ∼250-kDa, ∼160-Å polyglycosylated heterotetrameric particle with a remarkable glycan structure. Two FB moieties insert like wedges through a “CPDCP trunk” and two hairpins into the respective peptidase catalytic domains, blocking the catalytic zinc ions through an “aspartate switch” mechanism. Uniquely, the …
Novel mutations of the ABCA12, KRT1 and ST14 genes in three unrelated newborns showing congenital ichthyosis.
2022
Abstract Background Congenital ichthyosis (CI) is a heterogeneous group of genetic disorders characterized by generalized dry skin, scaling and hyperkeratosis, often associated to erythroderma. They are rare diseases, with overall incidence of 6.7 in 100,000. Clinical manifestations are due to mutations in genes mostly involved in skin barrier formation. Based on clinical presentation, CI is distinguished in non-syndromic and syndromic forms. To date, mutations of more than 50 genes have been associated to different types of CI. Cases presentation We report on three Italian unrelated newborns showing clinical signs compatible with different forms of CI of variable severity, namely Harlequin…
Signal transduction pathways of membrane expression of proteinase 3 (PR‐3) in human endothelial cells
1997
At present, the exact mechanism of the pathogenic effect of anti-PR-3 antibodies remains unknown. Interaction of anti-neutrophil cytoplasmic antibodies (ANCAs) with human umbilical vein endothelial cells (HUVECs) may play a key role. Recently we were able to show that ANCAs recognize their target antigen, PR-3, translocated into the membrane of HUVECs. The objective of this study was to investigate regulation, i.e. signal transduction pathways, of PR-3 expression in endothelial cells. HUVECs were isolated according to the method of Jaffe et al. and cultured under standard conditions. A cyto-enzyme-linked immunosorbent assay (ELISA) with unfixed cells was performed. Membrane-expressed PR-3 w…
Human endothelial cells express proteinase 3, the target antigen of anticytoplasmic antibodies in Wegener's granulomatosis
1993
Abstract Autoantibodies directed against cytoplasmic antigens of neutrophils (ANCA), especially proteinase 3 (PR-3), have proved to be a useful clinical tool confirming the diagnosis or monitoring disease activity of Wegener's granulomatosis (WG). Although several concepts concerning the pathophysiologic potentials of ANCA have been discussed, only sparse data about ANCA-endothelium interactions have been available. In this study, we have investigated the expression of PR-3 in cytokine- treated human endothelial cells using purified anti-PR-3 antibodies of patients with WG, murine and human monoclonal anti-PR-3 antibodies as probes. We were able to show that tumor necrosis factor-alpha, int…