Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The control of potentially periodontopathic microorganisms by host neutrophils is crucial to periodontal health. Neutrophils may use oxidative or nonoxidative mechanisms and either kill bacteria, influence bacterial growth, or modify bacterial colonization in the periodontium. Delivery of antimicrobial substances by neutrophils involves respiratory burst activity, phagocytosis, secretion, or cytolysis/apoptosis. Neutrophils contain a number of antimicrobial components including calprotectin complex, lysozyme, defensins, cofactor-binding proteins, neutral serine proteases, bactericidal/permeability increasing protein, myeloperoxidase, and a NADPH oxidase system. Many of these components are multifunctional and exhibit several mechanisms of antimicrobial activity. When comparisons are made among periodontal bacteria, differences in sensitivity to different components are observed. A hypothesis of specific defense is presented: That specific periodontal diseases can result from the failure of specific aspects of the host immune system (the neutrophil, in particular) in its interaction with specific periodontal pathogens. Failure may be due to phenotypic variation (pleomorphism) within the host or bacterial evasive strategies.
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PMID:The neutrophil: mechanisms of controlling periodontal bacteria. 176 39

Ligation of interleukin 2 (IL2) is known to regulate both protein tyrosine and serine/threonine phosphorylation. A family of leukocyte transmembrane proteins whose cytoplasmic domain exhibits intrinsic protein tyrosine phosphatase activity is collectively called CD45 and is identified by a set of common cell surface epitopes. Although CD45 is known to be a phosphoprotein, it is not known how phosphorylation specifically regulates its function. We therefore identified a cell line, the IL4-dependent line CTLL-2.4, in which CD45 could be phosphorylated in response to addition of IL2. These cells are a variant of an IL2-dependent murine cell line which were selected for long-term growth on IL4 but which retain the ability to proliferate on exposure to IL2. Incubation of CTLL-2.4 in low serum concentrations followed by stimulation with IL2 caused a three- to fivefold increase in the phosphorylation of CD45 in a time- and concentration-dependent manner. CD45 in non-stimulated cells contained one major tryptic phosphopeptide, whereas, after exposure of the cells to IL2, two new phosphopeptides were present in CD45. The pattern of IL2-induced phosphorylation was different from that found following addition of phorbol 12-myristate 13-acetate (PMA) to the cells. Although IL2 induced rapid and potent tyrosine phosphorylation in CTLL-2.4 cells, all of the basal and cytokine-activated phosphorylation of CD45 occurred on serine residues. The IL2-stimulated phosphorylation caused no change in the amount of cell surface CD45 and no alteration of its catalytic activity using an artificial tyrosine phosphorylated substrate-RCM-lysozyme. We speculate that the increase in phosphorylation of CD45 may modify its association with potential substrates. The differences in the phosphorylation patterns induced by IL2 and PMA further suggest that more than one kinase can use CD45 as substrate and that IL2 activates a protein serine/threonine kinase different from protein kinase C.
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PMID:Interleukin 2 stimulates serine phosphorylation of CD45 in CTLL-2.4 cells. 185 Mar 60

The physiologic substrates of cytotoxic T lymphocyte granule-associated serine esterases (referred to hereafter as proteases or "granzymes"), and the role of these enzymes in cell-mediated activity remain unclear. We have developed an assay for possible ligands of the trypsin-like dimeric serine protease granzyme A based on Western immunoblotting techniques. This protein-binding assay demonstrates the selective binding of granzyme A to several proteins present in the target cell P815. The binding specificity is preserved when enzyme binding is performed in the presence of excess competing proteins, including such cationic species as lysozyme and RNase. Enzyme binding is inhibited, however, by heat or detergent inactivation of granzyme A. Subcellular fractionation of target cells shows that the nuclear fraction contains most granzyme A binding reactivity, which is recovered in the nuclear salt wash fraction. A protein with Mr = 100,000 and two closely migrating proteins with Mr = 35,000 and 38,000 are the predominant reactive moieties, and the N-terminal sequence of the 100-kDa protein confirmed that this protein was murine nucleolin. Incubation of granzyme A with nucleolin generates a discrete proteolytic cleavage product of Mr = 88,000. Since nucleolin is known to shuttle between nucleus and cytoplasm, the interaction of granzyme A and nucleolin may be important in the process of apoptosis which accompanies cytotoxic T lymphocyte-mediated lysis of target cells.
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PMID:Granzyme A binding to target cell proteins. Granzyme A binds to and cleaves nucleolin in vitro. 186 Aug 69

Haemoglobin damaged by exposure of red blood cells to oxidants is rapidly degraded by a proteolytic pathway which does not require ATP [Fagan, Waxman & Goldberg (1986) J. Biol. Chem. 261, 5705-5713]. By fractionating erythrocyte lysates, we have purified two proteases which hydrolyse oxidatively damaged haemoglobin (Ox-Hb). One protease hydrolysed small fluorogenic substrates in addition to Ox-Hb. Its molecular mass was approximately 700 kDa and it consisted of several subunits ranging in size from 22 to 30 kDa. This enzyme may be related to the high-molecular-mass multicatalytic proteinase previously isolated from a variety of tissue and cell types. The other Ox-Hb-degrading activity had an apparent molecular mass of 400 kDa on gel filtration, a subunit size of 110 kDa and an isoelectric point between 4.5 and 5.0. This protease also hydrolysed the small polypeptides insulin and glucagon, as well as other large proteins such as lysozyme. Insulin blocked the degradation of Ox-Hb and Ox-Hb blocked the hydrolysis of insulin by the purified protease. Thiol reagents and metal chelators strongly inhibited the hydrolysis of both Ox-Hb and insulin, whereas inhibitors of serine, aspartic and thiol proteases had little effect. These properties suggest that the Ox-Hb-degrading activity purified from rabbit erythrocytes is the cytosolic insulin-degrading enzyme that is believed to play a role in the metabolism of insulin in several tissues. We propose that this enzyme may also function as a key component in a cytoplasmic degradative pathway responsible for removing proteins damaged by oxidants.
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PMID:Purification of a protease in red blood cells that degrades oxidatively damaged haemoglobin. 187 13

L-Canavanine is incorporated into the lysozyme synthesized, in response to administration of bacterial cell wall materials, by canavanine-treated larvae of the tobacco hornworm Manduca sexta (Sphingidae). Maximum canavanine incorporation into M. sexta lysozyme occurs when the larvae are provided 1 mg of canavanine g-1 fresh body weight. Analysis of canavanine-containing lysozyme purified from these insects reveals that 21% of the arginine residues are replaced by canavanine; this residue substitution results in a loss of 49.5% of the catalytic activity. When the larvae are provided 0.5 mg of canavanine g-1, 16.5% of the arginine residues are substituted by canavanine and 39.5% of the catalytic activity is lost. Canavanine is also incorporated into the lysozyme induced by canavanine-treated pupae of the giant silk moth Hyalophora cecropia (Saturnidae). In contrast, replacement of 17% of the arginine in H. cecropia lysozyme by canavanine fails to affect the catalytic activity. We have determined the primary structure of M. sexta lysozyme and compared it with the primary structure of H. cecropia lysozyme which has been described elsewhere. M. sexta lysozyme has an arginine at positions 23, 42, and 107. H. cecropia contains serine, lysine, and lysine, respectively, at these locations. The ability of incorporated canavanine to inhibit M. sexta lysozyme activity selectively may result from the fact that replacement of any one of the 3 arginine residues at position 23, 42, or 107 by canavanine causes the loss of catalytic activity.
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PMID:Studies of L-canavanine incorporation into insectan lysozyme. 187 26

The purpose of this study was to determine whether granule fractions of human neutrophils differentially kill Actinobacillus actinomycetemcomitans and Capnocytophaga spp. Granule extracts were subjected to gel filtration, and seven fractions (designated A through G) were obtained. Under aerobic conditions at pH 7.0, representative strains of A. actinomycetemcomitans were killed by fraction D and variably by fraction B. In contrast, the Capnocytophaga spp. were killed by fractions C, D, F, and G. Fractions A (containing lactoferrin and myeloperoxidase) and E (containing lysozyme) exerted little bactericidal activity under these conditions. Anaerobiosis had little effect on the bactericidal activity of fractions D and F but inhibited that of fractions B and C. Electrophoresis, zymography, determination of amino acid composition, and N-terminal sequence analysis revealed that fraction C contained elastase, proteinase 3, and azurocidin. Fraction D contained lysozyme, elastase, and cathepsin G. Subfractions of C and D containing elastase (subfraction C4), a mixture of elastase and azurocidin (subfraction C5), and cathepsin G (subfraction D9) were found to be bactericidal. The bactericidal effects of fraction D and subfraction D9 against A. actinomycetemcomitans was not inhibited by heat inactivation, phenylmethylsulfonyl fluoride, or N-benzyloxycarbonylglycylleucylphenylalanylchloromethyl ketone. We conclude that (i) A. actinomycetemcomitans and Capnocytophaga spp. were sensitive to the bactericidal effects of different neutrophil granule components, (ii) both were sensitive to the bactericidal effects of neutral serine proteases, and (iii) the killing of A. actinomycetemcomitans by cathepsin G-containing fractions was independent of oxygen and neutral serine protease activity.
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PMID:Differential killing of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. by human neutrophil granule components. 189 75

Packing interactions in bacteriophage T4 lysozyme were explored by determining the structural and thermodynamic effects of substitutions for Ala98 and neighboring residues. Ala98 is buried in the core of T4 lysozyme in the interface between two alpha-helices. The Ala98 to Val (A98V) replacement is a temperature-sensitive lesion that lowers the denaturation temperature of the protein by 15 degrees C (pH 3.0, delta delta G = -4.9 kcal/mol) and causes atoms within the two helices to move apart by up to 0.7 A. Additional structural shifts also occur throughout the C-terminal domain. In an attempt to compensate for the A98V replacement, substitutions were made for Val149 and Thr152, which make contact with residue 98. Site-directed mutagenesis was used to construct the multiple mutants A98V/T152S, A98V/V149C/T152S and the control mutants T152S, V149C and A98V/V149I/T152S. These proteins were crystallized, and their high-resolution X-ray crystal structures were determined. None of the second-site substitutions completely alleviates the destabilization or the structural changes caused by A98V. The changes in stability caused by the different mutations are not additive, reflecting both direct interactions between the sites and structural differences among the mutants. As an example, when Thr152 in wild-type lysozyme is replaced with serine, the protein is destabilized by 2.6 kcal/mol. Except for a small movement of Val94 toward the cavity created by removal of the methyl group, the structure of the T152S mutant is very similar to wild-type T4 lysozyme. In contrast, the same Thr152 to Ser replacement in the A98V background causes almost no change in stability. Although the structure of A98V/T152S remains similar to A98V, the combination of T152S with A98V allows relaxation of some of the strain introduced by the Ala98 to Val replacement. These studies show that removal of methyl groups by mutation can be stabilizing (Val98----Ala), neutral (Thr152----Ser in A98V) or destabilizing (Val149----Cys, Thr152----Ser). Such diverse thermodynamic effects are not accounted for by changes in buried surface area or free energies of transfer of wild-type and mutant side-chains. In general, the changes in protein stability caused by a mutation depend not only on changes in the free energy of transfer associated with the substitution, but also on the structural context within which the mutation occurs and on the ability of the surrounding structure to relax in response to the substitution.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Structural and thermodynamic analysis of the packing of two alpha-helices in bacteriophage T4 lysozyme. 192 Apr 39

Soluble reduced lysozyme was extensively digested by a trypsin-like protease purified from the culture supernatant of the bacterium. The digestion peptides were separated and purified by reversed-phase high-performance liquid chromatography, and were subjected to amino acid analysis. The fragments were identified by their amino acid composition, and the cleavage sites in the lysozyme chain were determined. Like mammalian trypsin, the enzyme from B. gingivalis split peptide bonds non-specifically at carboxyl sides of internal arginine and lysine residues, but the lysine present at the amino terminus of the lysozyme chain was not released. In addition, the enzyme cleaved the peptide linkage at the amino side of lysine and bonds between leucine-glycine, alanine-leucine and leucine-serine. Thus the trypsin-like protease from B. gingivalis has some cleavage actions on lysozyme different from those of mammalian trypsin.
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PMID:Cleavage action of a trypsin-like protease from Bacteroides gingivalis 381 on reduced egg-white lysozyme. 251 80

After exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA), cells of the promyelocytic leukemia cell line, HL-60, differentiate into macrophage-like cells. Within 24 h the cells adhere to the surface of the culture flask and increase production of nonspecific esterases. The intracellular concentration of the serine proteases increases two- to threefold within 4 days and continues to increase as the cells develop into mature macrophages. The acid hydrolases, lysozyme and beta-glucuronidase, were secreted by the differentiated cells. Both the intracellular and extracellular concentrations of these enzymes continued to increase as the cells matured. The fully differentiated cells readily phagocytized opsonized yeast cells. Phagocytosis had little effect on the secretion of acid hydrolases, while intracellular proteases increased significantly. The fully differentiated HL-60 cells resembled normal macrophages regarding all parameters studied. Viability of the differentiated cells exceeded 50% when cultured for 30 days. Therefore, these cells should prove to be a useful tool for the study of macrophage function with respect to microorganisms that are resistant to destruction by phagocytic cells.
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PMID:Long-term culturing of TPA-induced differentiated HL-60 cells results in increased levels of lytic enzymes. 267 May 94

A novel bacterial protease specifically hydrolyzing actin with the formation of a stable fragment with Mr of 36 kDa was obtained. This protease was shown to be synthesized at the stationary phase of bacterial culture growth. The actin hydrolysis by bacterial protease was inhibited by o-phenanthroline, EDTA and p-chloromercuribenzoate but not by N-ethyl-maleimide, phenylmethylsulfonylfluoride, Leu-peptin, pepstatin and other serine proteinase inhibitors. The protease was stable within the pH range of 4.5-8.5 and had an activity optimum at pH 7.0-8.0. The protease activity was maintained for 40 min at 45 degrees C and for 30 min at 50 degrees C; at 65 degrees C the enzyme was fully inactivated by 5 min heating. The protease preparations causing quantitative conversion of actin into a 36 kDa fragment did not hydrolyze casein, albumin, ovalbumin, lysozyme, DNAase I, RNAase, myosin, alpha-actinin, tropomyosin and troponin. It was assumed that the protease under consideration is a neutral metalloprotease specifically hydrolyzing actin.
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PMID:[Protease from a strain of bacteria E. coli A2, specifically cleaving actin]. 268 80


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