Search results for "Protease"
showing 10 items of 463 documents
α-Secretase Activity of the Disintegrin Metalloprotease ADAM 10: Influences of Domain Structure
2001
Disintegrin metalloproteases from different organisms form the ADAM (a disintegrin and metalloprotease) family. All members display a common domain organization and possess four potential functions: proteolysis, cell adhesion, cell fusion, and cell signaling. Members of the ADAM family are responsible for the proteolytic cleavage of transmembrane proteins and release of their extracellular domain. The proteolytic process is referred to as ectodomain shedding, which is activated by phorbol esters and inhibited by hydroxamic acid-based inhibitors. We have shown that the disintegrin metalloprotease ADAM 10 has both constitutive and regulated alpha-secretase activity. Expression of a dominant n…
Dipeptidyl Nitroalkenes as Potent Reversible Inhibitors of Cysteine Proteases Rhodesain and Cruzain.
2016
Dipeptidyl nitroalkenes are potent reversible inhibitors of cysteine proteases. Inhibitor 11 resulted to be the most potent one with Ki values of 0.49 and 0.44 nM against rhodesain and cruzain, respectively. According to enzymatic dilution and dialysis experiments, as well as computational and NMR studies, dipeptidyl nitroalkenes are tightly binding covalent reversible inhibitors. We thank Fundacion Española para la Ciencia y la Tecnología (Fecyt) and Generalitat Valenciana (AICO/2016/32) for financial support. T S. and B.E. thank the DFG (Deutsche Forschungsgemeinschaft) in the framework of the SFB630 for financial support. We thank Universitat Jaume I for technical suppport and funding. U…
Advances in the understanding of mast cell function
2008
Mast cells were formerly thought to contribute mainly to, sometimes even, fatal allergic reactions through the release of biologically highly active cytokines, chemokines, lipid mediators, proteases and biogenic amines. This potential harmful response is triggered by crosslinking of cell-bound IgE by the respective allergen. This review updates our current understanding of the emerging roles of mast cells with an emphasis on their relevance in protective host immunity. The activation of mast cells independently of Immunoglobulin E can lead to the initiation of fast inflammatory reactions, which were shown to be life-saving in murine models of bacterial infections. Besides their critical fun…
Purification and Characterization of <I>Bacillus cereus</I> Protease Suitable for Detergent Industry
2005
An extracellular alkaline protease from an alkalophilic bacterium, Bacillus cereus, was produced in a large amount by the method of extractive fermentation. The protease is thermostable, pH tolerant, and compatible with commercial laundry detergents. The protease purified and characterized in this study was found to be superior to endogenous protease already present in commercial laundry detergents. The enzyme was purified to homogeneity by ammonium sulfate precipitation, concentration by ultrafiltration, anion-exchange chromatography, and gel filtration. The purified enzyme had a specific activity of 3256.05 U/mg and was found to be a monomeric protein with a molecular mass of 28 and 31 kD…
Adsorption of proteins on porous and non-porous poly(ethyleneimine) and tentacle-type anion exchangers
1990
Abstract Adsorption isotherms of proteins [bovine serum albumin (BSA), soybean trypsin inhibitor and alcohol dehydrogenase] on anion exchangers were measured by on-line and off-line methods. The poly(ethyleneimine) (PEI) type and the tentacle-type materials exhibited principally different modes of adsorption. On thin layers of PEI, bonded to non-porous silica, BSA adsorption data corresponded to a monolayer of molecules, with 80% adsorbed side-on, with a high affinity constant for binding, and 20% adsorbed more weakly. With porous material, the amount of BSA bound per unit surface with high affinity was smaller. With tentacle-type anion exchangers, adsorption exceeded a monolayer by far, an…
The human gene for mannan-binding lectin-associated serine protease-2 (MASP-2), the effector component of the lectin route of complement activation, …
2001
The proteases of the lectin pathway of complement activation, MASP-1 and MASP-2, are encoded by two separate genes. The MASP1 gene is located on chromosome 3q27, the MASP2 gene on chromosome 1p36.23-31. The genes for the classical complement activation pathway proteases, C1r and C1s, are linked on chromosome 12p13. We have shown that the MASP2 gene encodes two gene products, the 76 kDa MASP-2 serine protease and a plasma protein of 19 kDa, termed MAp19 or sMAP. Both gene products are components of the lectin pathway activation complex. We present the complete primary structure of the human MASP2 gene and the tight cluster that this locus forms with non-complement genes. A comparison of the …
Phenoloxidase characterization in vacuolar hemocytes from the solitary ascidian Styela plicata
1995
Phenoloxidase (PO) activity was shown in lysates of Styela plicata hemocytes assayed spectrophotometrically by means of L-Dopa oxidation without divalent cations. Trypsin and chymotrypsin pretreatment and preincubation with microbial lipopolysaccharides significantly activated PO, whereas laminarin or zymosan were ineffective. Soybean trypsin inhibitor, tropolone, and phenylthiourea, but not benzamidine, were inhibitors. Finally, hemocytes were separated by a discontinuous Percoll density gradient to determine which cells were active. PO activity was demonstrated, by both biochemical and cytochemical assays, in the separated fraction enriched mainly with the globular granulocytes called mor…
Two Latent and Two Hyperstable Polymeric Forms of Human Neuroserpin
2010
AbstractHuman neuroserpin (hNS) is a serine protease inhibitor that belongs to the serpin superfamily and is expressed in nervous tissues. The serpin fold is generally characterized by a long exposed loop, termed the reactive center loop, that acts as bait for the target protease. Intramolecular insertion of the reactive center loop into the main serpin β-sheet leads to the serpin latent form. As with other known serpins, hNS pathological mutants have been shown to accumulate as polymers composed of quasi-native protein molecules. Although hNS polymerization has been intensely studied, a general agreement about serpin polymer organization is still lacking. Here we report a biophysical chara…
Molecular Classification of N-Aryloxazolidinone-5-carboxamides as Human Immunodeficiency Virus Protease Inhibitors
2015
Algorithms for classification and taxonomy are proposed in this chapter based information entropy (IE) and its production. The 38 N- aryloxazolidinone-5-carboxamides (NCAs), for human immunodeficiency virus (HIV) protease (PR) inhibition, are classified using seven characteristic chemical properties of different moieties: R 1/2 , R 3–6 on different phenyls and R 7 . Many classification algorithms are based on IE. When applying some procedures to moderate-sized sets, excessive number of results appear compatible with the data and suffer combinatorial explosion. However, after the equipartition conjecture (EC), one has a selection criterion among different variants that results from classifi…
Structure‐Activity Relationships of Benzamides and Isoindolines Designed as SARS‐CoV Protease Inhibitors Effective against SARS‐CoV‐2
2020
Abstract Inhibition of coronavirus (CoV)‐encoded papain‐like cysteine proteases (PLpro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure‐activity relationships (SAR) of the noncovalent active‐site directed inhibitor (R)‐5‐amino‐2‐methyl‐N‐(1‐(naphthalen‐1‐yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS‐CoV PLpro. Moreover, we report the discovery of isoindolines as a new class of potent PLpro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS‐CoV‐2 replication in …