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861.
Lise Boon Estefania Ugarte-Berzal Jennifer Vandooren 《Critical reviews in biochemistry and molecular biology》2020,55(2):111-165
AbstractProteases are a diverse group of hydrolytic enzymes, ranging from single-domain catalytic molecules to sophisticated multi-functional macromolecules. Human proteases are divided into five mechanistic classes: aspartate, cysteine, metallo, serine and threonine proteases, based on the catalytic mechanism of hydrolysis. As a protective mechanism against uncontrolled proteolysis, proteases are often produced and secreted as inactive precursors, called zymogens, containing inhibitory N-terminal propeptides. Protease propeptide structures vary considerably in length, ranging from dipeptides and propeptides of about 10 amino acids to complex multifunctional prodomains with hundreds of residues. Interestingly, sequence analysis of the different protease domains has demonstrated that propeptide sequences present higher heterogeneity compared with their catalytic domains. Therefore, we suggest that protease inhibition targeting propeptides might be more specific and have less off-target effects than classical inhibitors. The roles of propeptides, besides keeping protease latency, include correct folding of proteases, compartmentalization, liganding, and functional modulation. Changes in the propeptide sequence, thus, have a tremendous impact on the cognate enzymes. Small modifications of the propeptide sequences modulate the activity of the enzymes, which may be useful as a therapeutic strategy. This review provides an overview of known human proteases, with a focus on the role of their propeptides. We review propeptide functions, activation mechanisms, and possible therapeutic applications. 相似文献
862.
Adriana Oliveira Costa Isabela Aurora Rodrigues Chagas Armando de Menezes-Neto Felipe Dutra Rêgo Paula Monalisa Nogueira Ana Claudia Torrecilhas Cinthia Furst Blima Fux Rodrigo Pedro Soares 《Cell biology international》2021,45(5):1060-1071
Free living amoeba of the genus Acanthamoeba are opportunist protozoan involved in corneal, systemic, and encephalic infections in humans. Most of the mechanisms underlying intraspecies variations and pathogenicity are still unknown. Recently, the release of extracellular vesicles (EVs) by Acanthamoeba was reported. However, comparative characterization of EVs from distinct strains is not available. The aim of this study was to evaluate EVs produced by Acanthamoeba from different genotypes, comparing their proteases profile and immunomodulatory properties. EVs from four environmental or clinical strains (genotypes T1, T2, T4, and T11) were obtained by ultracentrifugation, quantitated by nanoparticle tracking analysis and analyzed by scanning and transmission electron microscopy. Proteases profile was determined by zymography and functional properties of EVs (measure of nitrite and cytokine production) were determined after peritoneal macrophage stimulation. Despite their genotype, all strains released EVs and no differences in size and/or concentration were detected. EVs exhibited a predominant activity of serine proteases (pH 7.4 and 3.5), with higher intensity in T4 and T1 strains. EVs from the environmental, nonpathogenic T11 strain exhibited a more proinflammatory profile, inducing higher levels of Nitrite, tumor necrosis factor alpha and interleukin-6 via TLR4/TLR2 than those strains with pathogenic traits (T4, T1, and T2). Preincubation with EVs treated with protease inhibitors or heating drastically decreased nitrite concentration production in macrophages. Those data suggest that immunomodulatory effects of EVs may reflect their pathogenic potential depending on the Acanthamoeba strains and are dependent on protease integrity. 相似文献
863.
J Jarosz 《Journal of invertebrate pathology》1979,34(2):192-198
Streptococcus faecalis, the only bacterium occurring almost invariably at high populations in guts of Galleria mellonella larvae, suppresses bacteria ingested with food by producing bacteriocin, an antibioticlike substance having a narrow range of bactericidal activity, and by releasing a lysozymelike enzyme, especially in the presence of proteolytic enzymes. The insect intestinal fluid apparently increases the activity of S. faecalis lytic enzyme. Unlike other organisms tested, S. faecalis has shown a strong bactericidal action against various species of unrelated bacteria. Microscopical examination of the sensitive organisms used as indicators has revealed changes resembling formation of protoplasts, gradually leading to destruction of bacterial cells. The insect guts could not be infected, even when the larvae had ingested a high dose of Pseudomonas aeruginosa, Proteus mirabilis, or Bacillus thuringiensis. The mechanism by which S. faecalis could suppress the ingested bacteria is suggested. 相似文献
864.
María Eugenia Errasti María José Torres Julio Ricardo Mercerat Néstor Oscar Caffini Laura María Isabel López 《Biocatalysis and Biotransformation》2020,38(5):357-366
AbstractIn the leather industry, proteases can be used as tools to achieve cleaner technology. In the present study, proteolytic preparations obtained from the latex of Carica papaya (Cp) and Vasconcellea quercifolia (Vq) were assayed as dehairing agents for leather processing. Both Cp and Vq showed activity against substrates representative of collagen, keratin, elastin, and epidermis in a range of moderate temperatures (25 to 55?°C). When comparing with a commercial dehairing enzyme, the activity of Cp and Vq on the substrates representative of epidermis and collagen was of around 70% and 100% of the commercial one, respectively, with that of Cp being more keratinolytic. Both Cp and Vq were able to dehair cowhides at 25?°C for 24?h without adding Ca(OH)2 or Na2S, two harmful pollutants used in conventional dehairing, Cp being more effective than Vq. Scanning electron microscopy microphotographs showed epidermis and hair-free hides with clean pores and without significant damage on the grain surface. Further, no damage was detected in collagen fibres and both Cp and Vq showed a slight opening of collagen fibres. We concluded that both Cp and Vq could be used as tools for a cleaner technology in tanneries, either for lime- and sulphide-free dehairing or for the treatment and valorisation of protein waste. 相似文献
865.
866.
The purified proteolytic fraction of Schistosoma mansoni cercarial enzymes (PCF) was inhibited by Diisopropylphosphofluoridate (DFP). Its esterolytic activity was not affected by either of two specific active center reagents of proteolytic enzymes: (1) 1-chloro-3-tosylamido-7-ammo-2-heptanone (trypsin) and (2) l-1-tosylamido-2-phenylethyl chloromethyl ketone (chymotrypsin). Furthermore, PCF did not destroy the biological activity of bradykinin on the isolated guinea pig ileum, nor did it release bradykinin from purified dog plasma bradykininogen. 相似文献
867.
Summary A fast dynamic programming algorithm for the spatial superposition of protein structure without prior knowledge of an initial alignment has been developed. The program was applied to serine proteases, hemoglobins, cytochromes C, small copper-binding proteins, and lysozymes. In most cases the existing structural homology could be detected in a completely unbiased way. The results of the method presented are in general agreement with other studies. Applying our method, the different alignment results obtained by other authors for serine proteases and cytochromes C can be classified in terms of different alignment parameters such as gap penalties or cut-off length. Limitations of the method are discussed. 相似文献
868.
869.
Prolidase deficiency (PD) is a rare inborn disorder of collagen metabolism characterized by chronic recurrent cutaneous ulceration. We report a novel 3 bp insertion in the 12th exon of the PEPD gene in two Kashmiri siblings with prolidase deficiency phenotype. This mutation results in addition of an extra alanine residue at the amino-acid position number 304 of prolidase peptide. The structural analysis showed that this Ala insertion is located at the helix (a.a. 300–320), which contains several important hydrogen bonds between residues essential for structural folding for the enzyme activity. In silico analysis suggests that this insertion mutation might distort or bend the helical feature to affect the hydrogen-bond network between residues of neighboring secondary structures and deform the metal-binding geometry of the enzyme. Although approximately 70 PEPD gene mutations and polymorphisms have been reported in various ethnic groups, we however report, for the first time, the identification of insertion mutation in human the PEPD gene. 相似文献
870.
Martine Urrutigoity Michel Baboulene J rome Souppe 《Biocatalysis and Biotransformation》1993,7(4):289-295
In an attempt to alter the catalytic properties of horseradish peroxidase (HRP, EC 1.11.1.7), aspartic, glutamic and arginine residues were modified using ethanedithiol and diacetyl. Modification of Asp and Glu led to a marked increase in Vmax along with denaturation of the protein. The thiol groups introduced were thought to be responsible, despite being situated on the periphery of the molecule as shown by the modification of the apoenzyme. The role of Arg 38 in the activation of hydrogen peroxide was indicated by the modifications of both enzyme and apoenzyme. An amino acid residue close to Arg 38 was thought to take over its function after blocking the group. 相似文献