Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Rats were exposed to nickel sulfate (NiSO4) either by intratracheal (IT) instillation or by acute aerosol inhalation, and pulmonary clearance of Ni and pulmonary inflammatory responses were studied. The half-time of Ni in the lung (initial lung burden = 50 micrograms Ni/rat) was about 32 h in both the IT instillation and inhalation groups. Ni retention in the lung tissue following IT instillation of NiSO4 was saturable with reference to dose, suggesting that clearance rate of Ni from the rat lung depends on lung burden of Ni. Lung inflammatory responses were evaluated by biochemical, elemental and cytological indicators in bronchoalveolar lavage fluid (BALF) following IT instillation of NiSO4. Activities of lactate dehydrogenase and beta-glucuronidase, contents of lysozyme, protein, sulfur and calcium, and the number of polymorphonuclear leukocytes were increased with a peak at 2-3 days post-instillation, while BALF alkaline phosphatase (ALP) activity was significantly decreased after IT instillation of NiSO4. Lung tissue ALP activity was also decreased by NiSO4. Because Ni does not inhibit ALP directly, the decrease in ALP activity is probably due to functional changes of type II cells (a major source of BALF ALP). Thiobarbituric acid reacting substances in the lung tissue were not changed by NiSO4, suggesting that lipid peroxidation plays a minimal, if any role, in the Ni-induced inflammation in the rat lung.
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PMID:Pulmonary clearance and inflammatory potency of intratracheally instilled or acutely inhaled nickel sulfate in rats. 799 20

1. Biochemical markers of kidney damage were examined in 14 male and 12 female workers highly exposed to soluble nickel compounds in a chemical plant. The results were compared to those obtained in 12 male and 12 female matched controls. 2. The concentration of nickel in urine of male and female workers averaged 5.0 and 10.3 micrograms g-1 creatinine, respectively. The mean duration of exposure in male and female workers was 25 and 15 years. 3. No difference was found in the mean urinary excretion of lactate dehydrogenase, albumin and transferrin in both sexes, total proteins, beta 2-microglobulin (beta 2-m) and retinol-binding protein (RBP) in males and lysozyme in females. Lysozyme and N-acetyl-beta-D-glucosaminidase (NAG) were increased in male and total proteins, beta 2-m, NAG and RBP in female exposed workers. Significant correlations between urinary concentrations of nickel on one side and that of beta 2-m in women (r = 0.462, P = 0.022) and men (r = 0.41, P = 0.018) and of NAG in men (r = 0.405, P = 0.019) on the other side were found in exposed subjects. 4. Results indicate adverse effects of soluble nickel compounds on the kidney tubular function. In agreement with literature data it seems that those effects occur only at high exposure levels.
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PMID:Biochemical renal changes in workers exposed to soluble nickel compounds. 820 11

Periplasmic expression of recombinant proteins presents many potential benefits that may aid recovery of the protein product. Muramidases are the preferred agents in effecting selective release of recombinant proteins from the periplasm of E. coli and other Gram negative bacteria. Unfortunately cost restricts the use of pure lytic enzymes at large-scale and their removal as process contaminants adds to later purification demands. We constructed a reusable version of bacteriophage T4 lysozyme, by fusing a His-Gln-(His)3 peptide sequence to the C-terminus of a cysteine-free pseudo wild type bacteriophage T4 lysozyme. The peptide tail allowed rapid and high-level recovery on IDA Sepharose columns charged with Zn2+, Ni2+ and Cu2+ ions. The binding to metal-charged supports was specifically mediated by the histidine-rich tail as no binding was observed for the original cysteine-free pseudo wild type lysozyme. The strength of retention of polyhistidine recombinant T4 lysozyme on charged supports followed the expected Cu > Ni > Zn pattern, but there were few differences in the levels of purity and recovery of the modified enzyme, from columns charged with the different metal ions.
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PMID:Expression and purification of a recombinant metal-binding T4 lysozyme fusion protein. 887 73

The chromatographic selectivity of the immobilized chelate system, 1,4,7-triazocyclononane (tacn), complexed with the borderline metal ions Cu2+, Cr3+, Mn2+, Co2+, Zn2+, and Ni2+ has been investigated with hen egg white lysozyme, horse heart cytochrome c, and horse skeletal muscle myoglobin, as well as proteins present in partially fractionated preparations of human plasma. The effects of ionic strength and pH of the loading and elution buffers on protein selectivities of these new immobilized metal ion affinity chromatographic (IMAC) systems have been examined. The results confirm that immobilized Mn;pl-tacn sorbents exhibit a novel type of IMAC behavior with proteins. In particular, the chromatographic properties of these immobilized M(n+)-tacn ligand systems were significantly different compared to the IMAC behavior observed with other types of immobilized tri- and tetradentate chelating ligands, such as iminodiacetic acid, O-phosphoserine, or nitrilotriacetic acid, when complexed with borderline metal ions. The experimental results have consequently been evaluated in terms of the additional contributions to the interactive processes mediated by effects other than solely the conventional lone pair Lewis soft acid-Lewis soft base coordination interactions, typically found for the IMAC of proteins with borderline and soft metal ions, such as Cu2+ or Ni2+.
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PMID:Protein selectivity with immobilized metal ion-tacn sorbents: chromatographic studies with human serum proteins and several other globular proteins. 944 41

It is not easy to find candidate sites within a given protein where the geometry of the polypeptide chain matches that of metal-binding sites in known protein structures. By choosing a location in T4 lysozyme that is inherently flexible, it was possible to engineer a two-histidine site that binds different divalent cations. Crystallographic analysis shows that the geometry of binding of zinc is distorted tetrahedral while that of cobalt and nickel is octahedral. Insofar as spectroscopic data can be measured, they indicate that similar modes of coordination are retained in solution. The two substitutions, Thr21 --> His and Thr142 --> His, lie, respectively, on the surface of the N- and C-terminal domains on opposite sides of the active site cleft. The design takes advantage of hinge-bending motion which allows the binding site to adapt to the most favorable ligand geometry for the metal. Introduction of the two histidines increases the melting temperature of the protein by 2.0 degrees C at pH 7.4. Metal binding further increases the melting temperature, but only by a small amount (up to 1.5 degrees C). A third substitution, Gln141 --> His, which could act as a third ligand in principle, does not do so, demonstrating the difficulty in mimicking naturally occurring metal-binding sites.
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PMID:Use of a non-rigid region in T4 lysozyme to design an adaptable metal-binding site. 1083 4

In a previous study, we used the genome of serogroup B Meningococcus to identify novel vaccine candidates. One of these molecules, GNA33, is well conserved among Meningococcus B strains, other Meningococcus serogroups and Gonococcus and induces bactericidal antibodies as a result of being a mimetic antigen of the PorA epitope P1.2. GNA33 encodes a 48-kDa lipoprotein that is 34.5% identical with membrane-bound lytic transglycosylase A (MltA) from Escherichia coli. In this study, we expressed GNA33, i.e. Meningococcus MltA, as a lipoprotein in E. coli. The lipoprotein nature of recombinant MltA was demonstrated by incorporation of [3H]palmitate. MltA lipoprotein was purified to homogeneity from E. coli membranes by cation-exchange chromatography. Muramidase activity was confirmed when MltA was shown to degrade insoluble murein sacculi and unsubstituted glycan strands. HPLC analysis demonstrated the formation of 1,6-anhydrodisaccharide tripeptide and tetrapeptide reaction products, confirming that the protein is a lytic transglycosylase. Optimal muramidase activity was observed at pH 5.5 and 37 degrees C and enhanced by Mg2+, Mn2+ and Ca2+. The addition of Ni2+ and EDTA had no significant effect on activity, whereas Zn2+ inhibited activity. Triton X-100 stimulated activity 5.1-fold. Affinity chromatography indicated that MltA interacts with penicillin-binding protein 2 from Meningococcus B, and, like MltA from E. coli, may form part of a multienzyme complex.
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PMID:GNA33 from Neisseria meningitidis serogroup B encodes a membrane-bound lytic transglycosylase (MltA). 1215 69

We found that the maximum emission of the tryptophyl fluorescence of hen egg-white lysozyme is shifted from 337 to 323 nm and quenched to the extent of 55% with an increase in concentrations of NiCl2 from 0 to 2M in 50 mM Na acetate buffer (pH 4.7). In contrast, NaCl does not influence the fluorescence of lysozyme up to 2M. To elucidate the particular effects of Ni2+ on the tryptophyl fluorescence of lysozyme, we have measured the assembly behavior and secondary structure of lysozyme in various concentrations of NiCl2, and determined the structures of lysozyme crystals grown in 0.3, 0.5, and 1.0M NiCl2, respectively. The results of analytical centrifugation and circular dichroism experiments show that lysozyme keeps a monomer state and has an identical secondary structure, irrespective of NiCl2 concentrations. The crystal structures show that all crystals grown in different concentrations of NiCl2 have an identical main chain and side chain conformation. And one Ni2+ binding with Odelta atom of Asp52 in the active site and coordinating with five water molecules to form hexagonal coordination has been determined for each crystal structure. Based on these results, we have proposed that Ni2+ quenches the fluorescence of Trp62 and Trp108 due to the binding of Ni2+ to the active site of lysozyme.
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PMID:Ni2+ binds to active site of hen egg-white lysozyme and quenches fluorescence of Trp62 and Trp108. 1547 59

The macrocyclic antiviral drug xylyl-bicyclam blocks entry of HIV into cells by targeting the CXCR4 coreceptor, a seven-helix transmembrane G-protein-coupled receptor. Its affinity for CXCR4 is enhanced by binding to Cu2+, Ni2+, or Zn2+. Metallocyclams have a rich configurational chemistry and proteins may bind selectively to specific metallocyclam configurations. Our studies of lysozyme reveal structural details of protein-metallocyclam interactions that are important for receptor recognition. Solution NMR studies show that Cu-cyclam interacts with specific tryptophan residues of lysozyme (Trp-62, Trp-63, and Trp-123). Two major binding sites for both Cu-cyclam and Cu2-xylyl-bicyclam were detected by x-ray crystallography. In the first site, Cu2+ in one cyclam ring of Cu2-xylyl-bicyclam adopts a trans configuration and is coordinated to a carboxylate oxygen of Asp-101, whereas for Cu-cyclam two ring NH groups form H bonds to the carboxylate oxygens of Asp-101, stabilizing an unusual cis (folded) cyclam configuration. For both complexes in this site, a cyclam ring is sandwiched between the indole side chains of two tryptophan residues (Trp-62 and Trp-63). In the second site, a trans cyclam ring is stacked on Trp-123 and H bonded to the backbone carbonyl of Gly-117. We show that there is a pocket in a model of the human CXCR4 coreceptor in which trans and cis configurations of metallobicyclam can bind by direct metal coordination to carboxylate side chains, cyclam-NH...carboxylate H bonding, together with hydrophobic interactions with tryptophan residues. These studies provide a structural basis for the design of macrocycles that bind stereospecifically to G-coupled and other protein receptors.
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PMID:Protein recognition of macrocycles: binding of anti-HIV metallocyclams to lysozyme. 1570 2

Metal binding to lysozyme has received wide interest. In particular, it is interesting that Ni2+, Mn2+, Co2+, and Yb3+ chloride salts induce an increase in the solubility of the tetragonal form in crystals of hen egg white lysozyme at high salt concentration, but that Mg2+ and Ca2+ chloride salts do not. To investigate the interactions of the di- and trivalent metal ions with the active site of lysozyme and compare the effects of the di- and trivalent metal ions on molecular conformation of lysozyme based on the structural analysis, the crystal structures of hen egg white lysozyme grown at pH 4.6, in the presence of 0.5 M MgCl2, CaCl2, NiCl2, MnCl2, CoCl2, and YbCl3, have been determined by X-ray crystallography at 1.58 A resolution. The crystals grown in these salts have an identical space group, P4(3)2(1)2. The molecules show no conformational changes, irrespective of the salts used. Ni2+ and Co2+ binding to the Odelta atom of Asp52 in the active site at 1.98 and 2.02 A, respectively, and Yb3+ binding to both the Odelta atom of Asp52 and the Odelta1 atom of Asn46 at 2.25 A have been identified. The binding sites of Mn2+, Mg2+, and Ca2+ have not been found from different Fourier electron density maps. The Ni2+ and Co2+ ions bind to the Odelta atom of Asp52 at almost the same position, while the Yb3+ ion takes a different position from the Ni2+ and Co2+ ions. On the other hand, the anion Cl-, interacting with the Oeta atom of Tyr23 at a site of about 2.90 A, has also been determined for each crystal.
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PMID:Structural details at active site of hen egg white lysozyme with di- and trivalent metal ions. 1613 73

Nickel(II)-xylylbicyclam is a potent anti-HIV agent and binds strongly to the CXCR4 co-receptor. We have investigated configurational equilibria of Ni(II)-cyclam derivatives, since these are important for receptor recognition. Crystallographic studies show that both trans and cis configurations are readily formed: [Ni(cyclam)(OAc)(2)] x H(2)O adopts the trans-III configuration with axial monodentate acetates, as does [Ni(benzylcyclam)(NO(3))(2)] with axial nitrate ligands, whereas [Ni(benzylcyclam)(OAc)](OAc)2 x H(2)O has an unusual folded cis-V configuration with Ni(II) coordination to bidentate acetate. UV/Vis and NMR studies show that the octahedral trans-III configuration slowly converts to square-planar trans-I in aqueous solution. For Ni(II)-xylylbicyclam, a mixture of cis-V and trans-I configurations was detected in solution. X-ray diffraction studies showed that crystals of lysozyme soaked in Ni(II)-cyclam or Ni(II) (2)-xylylbicyclam contain two major binding sites, one involving Ni(II) coordination to Asp101 and hydrophobic interactions between the cyclam ring and Trp62 and Trp63, and the second hydrophobic interactions with Trp123. For Ni(II)-cyclam bound to Asp101, the cis-V configuration predominates.
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PMID:Configurations of nickel-cyclam antiviral complexes and protein recognition. 1712 Feb 66


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