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 deposition of antigens and immune complexes (IC) in the renal glomerulus is charge-dependent. The demonstration that molecules of net anionic charge, but with discrete positively charged regions, exhibit affinity for the glomerular basement membrane (GBM) extends this concept. Charge hybrid (polar) molecules were constructed by covalently coupling small polycations (lysozyme or linear poly-L-lysine chains with a mean of 17 and 20 residues) to larger polyanions (ovalbumin or human serum albumin (HSA]. Although the products were of overall net anionic charge they still bound to glomerular structures. Immunofluorescence studies performed after i.v. injection of the samples into rats revealed that HSA:poly-L-lysine had the highest affinity. Radioisotopic measurements showed uptake of HSA:poly-L-lysine to be a function of the number of lysine residues; binding of HSA:poly-L-lysine20 was 2.5 times higher than HSA:poly-L-lysine17 (P less than 0.01). Prior injection of a small competing polycation (polyethyleneimine 1200) reduced uptake of HSA:poly-L-lysine by 75%, indicating the charge-based nature of the interaction. HSA:poly-L-lysine20 alone was effectively eliminated from the glomeruli within 72 h. Administration of HSA:poly-L-lysine followed by anti-HSA antibody induced immune complex formation in the capillary wall, giving rise to a granular immunofluorescence pattern and discrete subendothelial and subepithelial deposits. Molecules with polar structure do occur naturally and may contribute to immune complex formation in glomerulonephritis.
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PMID:Surface charge distribution is a determinant of antigen deposition in the renal glomerulus: studies employing 'charge-hybrid' molecules. 174 55

Low molecular weight proteins (LMWPs), such as lysozyme, may be suitable carriers to target drugs to the kidney. In this study the antiinflammatory drug naproxen was covalently bound to lysozyme (1:1). Pharmacokinetics of the conjugate, naproxen-lysozyme (nap-LYSO), were compared to that of an equimolar mixture of uncoupled naproxen with lysozyme in freely moving rats. Similar plasma kinetics and organ distribution for native lysozyme and the drug conjugate were observed (Clp = 1.2 and 1.1 ml/min; t1/2,beta = 85 and 75 min, respectively). In case of the uncoupled naproxen-lysozyme mixture, a monoexponential plasma disappearance of naproxen with a t1/2 of 2.8 hr was observed, coinciding with urinary excretion of naproxen metabolites (mainly 6-desmethylnaproxen sulfate; 6-DMN-S) between 2 and 8 hr after injection. Urinary recovery of total metabolites was 59% of the naproxen dose. In contrast, after injection of covalently bound naproxen, plasma levels of the parent drug were below the detection level, whereas naproxen was recovered as 6-DMN-S in urine over a period from 4 to 30 hr. However, only 8% of the administered dose was recovered as 6-DMN-S in urine, whereas 50% of the dose was recovered as naproxen metabolites in feces. Incubation experiments using purified renal tubular lysosomal lysates revealed that naproxen-lysozyme degradation ultimately results in a stable naproxen amino acid catabolite, naproxen-lysine (nap-lys). Hepatic uptake and biliary excretion of this catabolyte were demonstrated in isolated perfused rat livers. Further, an equipotent pharmacological activity relative to parent naproxen was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low molecular weight proteins as carriers for renal drug targeting: naproxen-lysozyme. 179 38

Fast atom bombardment mass spectrometry (FAB) was used to determine the glycation sites of lysozyme in a restricted water environment. A 30-day incubation at 25 degrees C, and 65% relative humidity (R.H.) resulted in glycation at lysine-1 while a much shorter (3-day) incubation at 50 degrees C and 65% R.H. resulted in diglycation at lysine-1 as well as glycation at lysine-13 and lysine-33.
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PMID:Glycation of lysozyme in a restricted water environment. 181 46

Regulation of cell growth and metabolism by protein tyrosine phosphorylation involves dephosphorylation via the action of protein tyrosine phosphatases (PTPases). We have characterized the membrane PTPases in rat liver, monitoring their activity by measuring the dephosphorylation of P-Tyr-reduced, carboxyamidomethylated and maleylated lysozyme (P-Tyr-RCML) and P-Tyr-myelin basic protein (P-Tyr-MBP). Separation of membrane PTPases by poly (L-lysine) chromatography yielded three peaks of PTPase, termed I, II and III. PTPases I and II were most active with P-Tyr-RCML, whereas PTPase III showed greater activity with P-Tyr-MBP than with P-Tyr-RCML (ratio of activities 4:1). Separation of membrane proteins by gel-filtration chromatography yielded two peaks of activity. Based on substrate specificity, sensitivity to inhibitors and requirement for thiol-containing compounds, the activity peak with an Mr of approximately 400,000 corresponded to PTPase III, whereas that with an Mr of approx. 40,000 contained PTPases I and II. All three PTPases dephosphorylated epidermal growth factor receptors and insulin receptors, but only PTPases I and II were active with P-Tyr-asialoglycoprotein receptors. Although none of the above characteristics distinguished between PTPases I and II, only PTPase I reacted in a Western immunoblotting procedure with anti-peptide antibodies directed towards human placental PTPase. We conclude that the membrane fraction from rat liver contains at least three distinct PTPases.
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PMID:Hepatic protein tyrosine phosphatases in the rat. 184 53

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

A fluorescent compound has been detected in proteins browned during Maillard reactions with glucose in vitro and shown to be identical to pentosidine, a pentose-derived fluorescent cross-link formed between arginine and lysine residues in collagen (Sell, D. R., and Monnier, V. M. (1989) J. Biol. Chem. 264, 21597-21602). Pentosidine was the major fluorophore formed during nonenzymatic browning of ribonuclease and lysozyme by glucose, but accounted for less than 1% of non-disulfide cross-links in protein dimers formed during the reaction. Pentosidine was formed in greatest yields in reactions of pentoses with lysine and arginine in model systems but was also formed from glucose, fructose, ascorbate, Amadori compounds, 3-deoxyglucosone, and other sugars. Pentosidine was not formed from peroxidized polyunsaturated fatty acids or malondialdehyde. Its formation from carbohydrates was inhibited under nitrogen or anaerobic conditions and by aminoguanidine, an inhibitor of advanced glycation and browning reactions. Pentosidine was detected in human lens proteins, where its concentration increased gradually with age, but it did not exceed trace concentrations (less than or equal to 5 mumol/mol lysine), even in the 80-year-old lens. Although its precise carbohydrate source in vivo is uncertain and it is present in only trace concentrations in tissue proteins, pentosidine appears to be a useful biomarker for assessing cumulative damage to proteins by nonenzymatic browning reactions with carbohydrates.
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PMID:Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo. 190 67

When assayed in vitro, the activity of the photosynthetic enzyme ribulose 1,5 bisphosphate carboxylase oxygenase is both enhanced and protected from spontaneous decay by exogenous proteins such as hemoglobin, serum albumin, and aldolase. Other proteins and amino acids tested are either ineffective (lysozyme, ferritin, lysine, and cysteine) or afford only partial protection (catalase, glycine, and phenylalanine). Protective proteins do not bind to, or exchange disulfides with, ribulose 1.5 bisphosphate carboxylase/oxygenase. Since their effect can be mimicked by reductively treated detergents such as Triton X-100, it appears that proteins protect from decay by quenching the spontaneous oxidative degradation and inhibiting surface adsorption which could lead to enzyme unfolding. Release of adsorbed molecules from the container surface is likely to be the cause of carboxylase activity enhancement.
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PMID:Protection and enhancement of ribulose 1,5 bisphosphate carboxylase activity by exogenous proteins. 191 Apr 60

The mechanism of reaction of proteins with 3-hydroxyanthranilic acid (3OHA) under oxidizing conditions has been examined. A range of proteins were found to tan when exposed to oxidized 3OHA. One exception was lysozyme which tanned only after being denatured by reduction and carboxymethylation. Chemical modification experiments using bovine serum albumin (BSA) suggested that lysine was the primary site of reaction in 3OHA-mediated protein tanning. This reactivity of 3OHA toward lysine was confirmed by autoxidizing 3OHA in the presence of amino acid homopolymers. The rate of modification of both BSA and polylysine was pH dependent. At neutral pH, a component of the coloration of the protein was found to be due to the formation of a lysyl-p-quinone adduct. Other products appear to arise through addition to the 3OHA quinone imine. Poly-(Glu,Lys) was tanned by 3OHA at a greatly reduced rate, suggesting that electrostatic interactions may influence the reaction with lysine residues and may provide an explanation for the lack of tanning of lysozyme. Despite the reaction between 3OHA and lysine, amino acid analysis revealed little quantitative change in the lysine content of proteins even after exposure to 3OHA for a period of 24 h. These results support the proposal that reaction with lysine residues is the major route of protein tanning by 3-hydroxyanthranilic acid.
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PMID:Modification of proteins by 3-hydroxyanthranilic acid: the role of lysine residues. 192 12

Several previous findings have suggested that the cationic nature of lysozyme is a major factor in its bactericidal activity. Since a number of cationic proteins or peptides have been reported to cause membrane damage in bacteria, we investigated the effect of lysozyme on glucose fermentation and intracellular pH and K+ in Streptococcus mutans under conditions in which lysis does not occur. Results showed that lysozyme and poly-D-lysine (PDL) cause inhibition of glucose fermentation at pH 5.5 in a dose-dependent manner. Human placental lysozyme and hen egg-white lysozyme exhibited similar inhibitory potency on glucose fermentation. Both lysozyme and PDL caused a marked acidification of the cytoplasm of S. mutans. However, when cytoplasmic pH was examined as a function of fermentation rate, the relationship was similar regardless of the presence or absence of lysozyme or PDL. Therefore, acidification of the cytoplasm appeared to not depend specifically on lysozyme or PDL. In contrast, the same relationship between the profound loss of intracellular K+, when fermenting cells were exposed to either lysozyme or PDL, and the fermentation rate was not exhibited in the controls. These results indicate that lysozyme and PDL specifically affected the ability of the cells to maintain intracellular K+. We concluded that lysozyme and PDL indeed perturb membrane function, perhaps in a selective manner. Furthermore, the similarity in action of lysozyme and the cationic homopolypeptide PDL supports the notion that the cationic property of lysozyme indeed plays a significant role in its antibacterial activity.
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PMID:Effect of lysozyme on glucose fermentation, cytoplasmic pH, and intracellular potassium concentrations in Streptococcus mutans 10449. 198 80

In a previous report from this laboratory (N. J. Laible and G. R. Germaine, Infect. Immun. 48:720-728, 1985), evidence was presented to suggest that the bactericidal actions of both reduced (i.e., muramidase-inactive) human placental lysozyme and the synthetic cationic homopolymer poly-D-lysine involved the activation of a bacterial endogenous activity that was inhibitable by N,N',N"-triacetylchitotriose (chitotriose). In the present investigation however, we found that the bactericidal and bacteriolytic action of poly-D-lysine could be prevented only by some commercially available chitotriose preparations and not by others. Analysis by physical and chemical methods failed to distinguish protective chitotriose (CTa) and nonprotective chitotriose (CTi) preparations. CTi and CTa preparations displayed equal capacities to competitively inhibit binding of [3H]chitotriose by immobilized lysozyme and were indistinguishable in their abilities to block the lytic activity of lysozyme against Micrococcus lysodeikticus cells. Elemental analysis revealed significantly higher levels of phosphorus, calcium, iron, sodium, manganese, and copper in CTa. Removal of metals from CTa by chelate chromatography completely abolished the poly-D-lysine-protective capacity. Of the metals detected, only ferric iron (5 to 10 microM) mimicked the protective action of CTa. A Fe(III) concentration of 50 microM was required to inhibit lysozyme (5 micrograms/ml). Both Fe(III) and CTa (but not CTi) quantitatively blocked the labeling of poly-D-lysine by fluorescamine, suggesting that the primary amino groups of the lysine residues participate in iron binding. Thus, it appears that the poly-D-lysine-protective capacity of certain chitotriose preparations was due not to the chitotriose itself but to contaminating metal ions which interact directly with the polycationic agent. In contrast, Fe(III) cannot account for inhibition of either the bactericidal or bacteriolytic activity of lysozyme by chitotriose.
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PMID:Inhibition of bactericidal and bacteriolytic activities of poly-D-lysine and lysozyme by chitotriose and ferric iron. 198 82


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