Search results for "Proteinase"
showing 10 items of 407 documents
Targeting of the Leishmania Mexicana cysteine protease CPB2.8 ΔCTE by decorated fused benzo[b] thiophene scaffold.
2016
A potent and highly selective anhydride-based inhibitor of Leishmania mexicana cysteine protease CPB2.8ΔCTE (IC50 = 3.7 μM) was identified. The details of the interaction of the ligand with the enzyme active site were investigated by NMR biomimetic experiments and docking studies. Results of inhibition assays, NMR and theoretical studies indicate that the ligand acts initially as a non-covalent inhibitor and later as an irreversible covalent inhibitor by chemoselective attack of CYS 25 thiolate to an anhydride carbonyl.
Age-dependent control of collagen-dependent platelet responses by thrombospondin-1 : Comparative analysis of platelets from neonates, children, adole…
2021
Platelet function is developmentally regulated. Healthy neonates do not spontaneously bleed, but their platelets are hypo-reactive to several agonists. The mechanisms underlying immature platelet function in neonates are incompletely understood. This critical issue remains challenging for the establishment of age-specific reference ranges. In this study, we evaluated platelet reactivity of five pediatric age categories, ranging from healthy full-term neonates up to adolescents (11–18 years) in comparison to healthy adults (>
Identification and structural characterization of LytU, a unique peptidoglycan endopeptidase from the lysostaphin family
2017
AbstractWe introduce LytU, a short member of the lysostaphin family of zinc-dependent pentaglycine endopeptidases. It is a potential antimicrobial agent for S. aureus infections and its gene transcription is highly upregulated upon antibiotic treatments along with other genes involved in cell wall synthesis. We found this enzyme to be responsible for the opening of the cell wall peptidoglycan layer during cell divisions in S. aureus. LytU is anchored in the plasma membrane with the active part residing in the periplasmic space. It has a unique Ile/Lys insertion at position 151 that resides in the catalytic site-neighbouring loop and is vital for the enzymatic activity but not affecting the …
Proteolytic Enzymes Clustered in Specialized Plasma-Membrane Domains Drive Endothelial Cells’ Migration
2016
In vitro cultured endothelial cells forming a continuous monolayer establish stable cell-cell contacts and acquire a "resting" phenotype; on the other hand, when growing in sparse conditions these cells acquire a migratory phenotype and invade the empty area of the culture. Culturing cells in different conditions, we compared expression and clustering of proteolytic enzymes in cells having migratory versus stationary behavior. In order to observe resting and migrating cells in the same microscopic field, a continuous cell monolayer was wounded. Increased expression of proteolytic enzymes was evident in cell membranes of migrating cells especially at sprouting sites and in shed membrane vesi…
Update on the role of molecular factors and fibroblasts in the pathogenesis of Dupuytren’s disease
2016
The mechanism by which the fibroblast is able to trigger palmar fibromatosis is still not yet fully understood. It would appear certain that the “abnormal” fibroblasts continuously synthesise profibrotic cytokines which are able to determine the activation to myofibroblasts, to stimulate them to the further proliferation and synthesis of other cytokines, to modify the cells’ differentiation and ultrastructural characteristics, as well as the production of matrix and other proteins. Several fibroblast growth factors have been suggested to be responsible of an abnormal cell activation with an aberrantly elevated collagen synthesis and extracellular deposition in Dupuytren’s disease, as TGF-Be…
Dipeptidyl Peptidase IV as a Muscle Myokine
2020
Dipeptidyl peptidase IV (DPP-IV) is a unique serine protease that exists in a membrane bound state and in a soluble state in most tissues in the body. DPP-IV has multiple targets including cytokines, neuropeptides, and incretin hormones, and plays an important role in health and disease. Recent work suggests that skeletal muscle releases DPP-IV as a myokine and participates in control of muscle blood flow. However, few of the functions of DPP-IV as a myokine have been investigated to date and there is a poor understanding about what causes DPP-IV to be released from muscle.
Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy.
2016
Various, diverse molecules contribute to the tumor microenvironment and influence invasion and metastasis. In this review, the roles of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) in the tumor microenvironment and sensitivity to therapy will be discussed. The lipocalin family of proteins has many important functions. For example when NGAL forms a complex with MMP-9 it increases its stability which is important in cancer metastasis. Small hydrophobic molecules are bound by NGAL which can alter their entry into and efflux from cells. Iron transport and storage are also influenced by NGAL activity. Regulation of iron levels is important for survival…
Specialized regulatory T cells control venous blood clot resolution through SPARC.
2020
Abstract The cells and mechanisms involved in blood clot resorption are only partially known. We show that regulatory T cells (Tregs) accumulate in venous blood clots and regulate thrombolysis by controlling the recruitment, differentiation and matrix metalloproteinase (MMP) activity of monocytes. We describe a clot Treg population that forms the matricellular acid– and cysteine-rich protein SPARC (secreted protein acidic and rich in cysteine) and show that SPARC enhances monocyte MMP activity and that SPARC+ Tregs are crucial for blood clot resorption. By comparing different treatment times, we define a therapeutic window of Treg expansion that accelerates clot resorption.
Ectodomain shedding of CD99 within highly conserved regions is mediated by the metalloprotease meprin β and promotes transendothelial cell migration.
2016
The adhesion molecule CD99 is essential for the transendothelial migration of leukocytes. In this study, we used biochemical and cellular assays to show that CD99 undergoes ectodomain shedding by the metalloprotease meprin β and subsequent intramembrane proteolysis by γ-secretase. The cleavage site in CD99 was identified by mass spectrometry within an acidic region highly conserved through different vertebrate species. This finding fits perfectly to the unique cleavage specificity of meprin β with a strong preference for aspartate residues and suggests coevolution of protease and substrate. We hypothesized that limited CD99 cleavage by meprin β would alter cellular transendothelial migratio…
The Metalloprotease Meprin β Is an Alternative β-Secretase of APP
2017
The membrane bound metalloprotease meprin β is important for collagen fibril assembly in connective tissue formation and for the detachment of the intestinal mucus layer for proper barrier function. Recent proteomic studies revealed dozens of putative new substrates of meprin β, including the amyloid precursor protein (APP). It was shown that APP is cleaved by meprin β in distinct ways, either at the β-secretase site resulting in increased levels of Aβ peptides, or at the N-terminus releasing 11 kDa, and 20 kDa peptide fragments. The latter event was discussed to be rather neuroprotective, whereas the ectodomain shedding of APP by meprin β reminiscent to BACE-1 is in line with the amyloid h…