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

---

Query: EC:3.2.1.17 (lysozyme)
21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Free energy simulation methods are used to analyse the effects of the mutation Arg-96----His on the stability of bacteriophage T4 lysozyme and of Ile-96----Ala on the stability of barnase. By use of thermodynamic integration, the contributions of specific interactions to the free energy change are evaluated. It is shown that a number of contributions that stabilize the wild-type or the mutant partially cancel in the overall free energy difference; some of these involve the unfolded state. Comparison of the results with conclusions based on structural and thermodynamic data leads to new insights into the origin of the stability difference between wild-type and mutant proteins. For the charged-to-charged amino acid mutation in T4 lysozyme, the importance of the contributions of more distant residues, solvent water and the covalent linkage involving the mutated amino acid are of particular interest. Also, the analysis of the Arg-96 to His mutation with respect to the interactions with the C-terminal end of a helix (residues 82-90) indicates that the nearby carbonyl groups (Tyr-88 and Asp-89) make the dominant contribution, that the amide groups do not contribute significantly and that the helix dipole model is inappropriate for this case. For the non-polar-to-non-polar amino acid mutation in barnase, the solvent contribution is unimportant, and covalent terms are shown to be significant because they do not cancel between the folded and unfolded state.
...
PMID:Simulation analysis of the stability mutants R96H of bacteriophage T4 lysozyme and I96A of barnase. 181 97

The partial molar volumes of various compounds that model protein constituent groups, such as tripeptides (Gly-X-Gly, where X = Gly, Ala, Val, Leu, Ile, Pro, Met, His, Ser), homopeptides (Glyn, n = 3,4,5), and simple organic analogues of amino acid side chains (methanol, acetamide, propanamide, acetic acid, propanoic acid, n-butanamine, n-butanamine nitrate, n-propylguanidine nitrate, 4-methylphenol), have been determined in aqueous solution with a vibrational densimeter in the temperature range of 5-85 degrees C. The partial molar volumes of amino acid side chains and the peptide unit were estimated from the data obtained. Assuming additivity of component groups, the partial molar volumes of polypeptide chains of several proteins over a broad temperature range were calculated. The partial molar volume functions of four proteins (myoglobin, cytochrome C, ribonuclease A, lysozyme) were compared with those determined experimentally for the unfolded and native forms of these proteins. It has been shown that the average deviation of the calculated functions from the experimental ones does not exceed 3% over the temperature range studied.
...
PMID:Partial molar volumes of polypeptides and their constituent groups in aqueous solution over a broad temperature range. 208 Dec 62

Paramagnetic agents produce line broadening and thus cancellation of anti phase cross-peak components in two-dimensional correlated nuclear magnetic resonance spectra. The specificity of this effect was examined to determine its utility for identifying surface residues of proteins. Ubiquitin and hen egg white lysozyme, for which X-ray crystal structures and proton NMR assignments are available, served as test cases. Two relaxation reagents were employed, 4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxy and the gadolinium (III) diethylenetriaminepentaacetate complex ion. Correlations were sought between reagent-produced decreases of side-chain cross-peak volumes in double-quantum-filtered proton correlation (DQF-COSY) spectra and the solvent-exposed side-chain surface area of the corresponding residues. The lanthanide complex produced strong effects ascribable to association with carboxylate groups but was not otherwise useful in delineating surface residues. The nitroxyl, on the other hand, produced clear distinctions among the Val, Leu, and Ile residues that generally paralleled side-chain exposure in the crystal, although consistent correlations were not observed with residues of other types. Although an instance of possible specific protein-nitroxyl association was noted, the nitroxyl appears to be a tool for identifying hydrophobic surface residues.
...
PMID:NMR identification of protein surfaces using paramagnetic probes. 217 60

The proton and nitrogen (15NH-H alpha-H beta) resonances of bacteriophage T4 lysozyme were assigned by 15N-aided 1H NMR. The assignments were directed from the backbone amide 1H-15N nuclei, with the heteronuclear single-multiple-quantum coherence (HSMQC) spectrum of uniformly 15N enriched protein serving as the master template for this work. The main-chain amide 1H-15N resonances and H alpha resonances were resolved and classified into 18 amino acid types by using HMQC and 15N-edited COSY measurements, respectively, of T4 lysozymes selectively enriched with one or more of alpha-15N-labeled Ala, Arg, Asn, Asp, Gly, Gln, Glu, Ile, Leu, Lys, Met, Phe, Ser, Thr, Trp, Tyr, or Val. The heteronuclear spectra were complemented by proton DQF-COSY and TOCSY spectra of unlabeled protein in H2O and D2O buffers, from which the H beta resonances of many residues were identified. The NOE cross peaks to almost every amide proton were resolved in 15N-edited NOESY spectra of the selectively 15N enriched protein samples. Residue specific assignments were determined by using NOE connectivities between protons in the 15NH-H alpha-H beta spin systems of known amino acid type. Additional assignments of the aromatic proton resonances were obtained from 1H NMR spectra of unlabeled and selectively deuterated protein samples. The secondary structure of T4 lysozyme indicated from a qualitative analysis of the NOESY data is consistent with the crystallographic model of the protein.
...
PMID:Assignment of the backbone 1H and 15N NMR resonances of bacteriophage T4 lysozyme. 220 79

Phage T4 lysozyme consists of two domains between which is formed the active-site cleft of the enzyme. The crystallographically determined thermal displacement parameters for the protein suggested that the amino terminal of the two domains undergoes 'hinge-bending' motion about an axis passing through the waist of the molecule. Such conformational mobility may be important in allowing access of substrates to the active site of the enzyme. We report here a crystallographic study of a mutant T4 lysozyme which demonstrates further the conformational flexibility of the protein. A mutant form of the enzyme with a methionine residue (Met 6) replaced by isoleucine crystallizes with four independent molecules in the crystal lattice. These four molecules have distinctly different conformations. The mutant protein can also crystallize in standard form with a structure very similar to the wild-type protein. Thus the mutant protein can adopt five different crystal conformations. The isoleucine for methionine substitution at the intersection of the two domains of T4 lysozyme apparently enhances the hinge-bending motion presumed to occur in the wild-type protein, without significantly affecting the catalytic activity or thermal stability of the protein.
...
PMID:A mutant T4 lysozyme displays five different crystal conformations. 223 88

Equilibrium and kinetic effects on the folding of T4 lysozyme were investigated by fluorescence emission spectroscopy in cryosolvent. To study the role of disulfide cross-links in stability and folding, a comparison was made with a mutant containing an engineered disulfide bond between Cys-3 (Ile-3 in the wild type) and Cys-97, which links the C-terminal domain to the N terminus of the protein [Perry & Wetzel (1984) Science 226, 555]. In our experimental system, stability toward thermal and denaturant unfolding was increased slightly as a result of the cross-link. The corresponding reduced protein was significantly less stable than the wild type. Unfolding and refolding kinetics were carried out in 35% methanol, pH 6.8 at -15 degrees C, with guanidine hydrochloride as the denaturant. Unfolding/refolding of the wild-type and reduced enzyme showed biphasic kinetics both within and outside the denaturant-induced transition region and were consistent with the presence of a populated intermediate in folding. Double-jump refolding experiments eliminated proline isomerization as a possible cause for the biphasicity. The disulfide mutant protein, however, showed monophasic kinetics in all guanidine concentrations studied.
...
PMID:Effect of an engineered disulfide bond on the folding of T4 lysozyme at low temperatures. 233 94

Multiple replacements at amino acid position 3 of bacteriophage T4 lysozyme have shown that the conformational stability of the protein is directly governed by the hydrophobicity of the residue substituted (Matsumura, M., Becktel, W. J., and Matthews, B. W. (1988) Nature 334, 406-410). Of the 13 mutant lysozymes made by site-directed mutagenesis, two variants, one with valine (I3V) and the other with tyrosine (I3Y), were crystallized and their structures solved. In this report we describe the crystal structures of these variants at 1.7 A resolution. While the structure of the I3V mutant is essentially the same as that of wild-type lysozyme, the I3Y mutant has substantial changes in its structure. The most significant of these are that the side chain of the tyrosine is not accommodated within the interior of the protein and the amino-terminal polypeptide (residues 1-9) moves 0.6-1.1 A relative to the wild-type structure. Using coordinates based on the wild-type and available mutant structures, solvent accessible surface area of residue 3 as well as the adjacent 9 residues in the folded form were calculated. The free energy of stabilization based on the transfer of these residues from a fully extended form to the interior to the folded protein was found to correlate well with the protein stability determined by thermodynamic analysis. The enhanced thermostability of the variant Ile-3----Leu, relative to wild-type lysozyme, can also be rationalized by surface-area calculations based on a model-built structure. Noncrystallization of most lysozyme variants at position 3 appears to be due to disruption of intermolecular contacts in the crystal. The Ile-3----Val variant is closely isomorphous with wild-type and maintains the same crystal contacts. In the Ile-3----Tyr variant, however, a new set of contacts is made in which direct protein-protein hydrogen bonds are replaced by protein-water-protein hydrogen bonds as well as a novel hydrogen bond involving the phenolic hydroxyl of the substituted tyrosine.
...
PMID:Structural studies of mutants of T4 lysozyme that alter hydrophobic stabilization. 267 24

Circular dichroism studies on synthetic peptides corresponding to the signal sequences of chicken lysozyme and Escherichia coli proteins, lambda-receptor and lipoprotein, have been carried out in trifluoroethanol. The peptides, (CH3)3-C-O-CO-Thr-Leu-Lys-Lys-Leu-Pro-Leu-Ala-Val-Ala-Val-Ala-Ala-Gly- Val-Met-Thr-Ala- Ala-Met-Ala-OCH3, (CH3)3-C-O-CO-Met-Lys-Ser-Leu-Leu-Ile-Leu-Val-Leu-Cys(benzyl)- Phe-Leu-Pro- Leu-Ala-Ala-Leu-Gly-OH and (CH3)3-C-O-CO-Leu-Val-Leu-Gly-Ala-Val-Ile-Leu-Gly- Thr-Thr-Leu-Leu- Ala-Gly-OCH3, corresponding to the signal sequences of lambda-receptor, lysozyme and the hydrophobic region of lipoprotein, respectively, show two negative bands at approx. 205 and 220 nm, characteristic of an alpha-helical conformation. Secondary structural features are discernible even in the shorter, 12-residue carboxy-terminal fragments of these signal peptides. A comparison of the conformation of the amino-terminal, central and carboxy-terminal fragments of lipoprotein signal sequence indicates that the central octapeptide fragment is more structurally ordered compared to the amino- and carboxy-terminal fragments.
...
PMID:Circular dichroism studies on synthetic signal peptides. 293 58

Solitary mastocytoma (mast cell naevus) of the skin represents a relatively rare dermal tumour. Its occurrence on the lower eyelid is exceptional. We report the case of a 4 month old male infant who exhibited a firm, yellowish nodule (1 cm in maximum diameter) on the lower lid of the right eye from birth. Histologically, the tumour consisted of strongly metachromatic tissue mast cells (TMC) infiltrating the whole dermis, the adjacent subcutaneous tissue and the lid muscle. Since comparable skin lesions in other sites were not observed, a diagnosis of solitary mastocytoma was made. Immunocytological investigations revealed strong reactivity of the TMC to antisera against vimentin, common leucocyte antigen (CLA), alpha 1-antitrypsin (alpha 1-AT) and alpha 1-antichymotrypsin (alpha 1-ACT). A minor proportion of the TMC reacted to antisera against lysozyme and KiB3. Surprisingly, the TMC also reacted to antisera against certain regulatory peptides (RP), namely adrenocorticotropic hormone (ACTH), peptide histidine isoleucine (PHI), leu-enkephalin and met-enkephalin. However, absorption controls revealed that the immunostaining for ACTH and the two enkephalins was non-specific. The immunocytological phenotype of TMC suggests a close relationship to the myeloid-monocytic lineage, but a possible relationship between TMC and the diffuse neuroendocrine system needs further investigation.
...
PMID:Solitary mastocytoma of the eyelid. A case report with special reference to the immunocytology of human tissue mast cells, and a review of the literature. 312 Apr 1

Immunoreactivity of human tissue mast cells (TMCs) was studied in one case of solitary mastocytoma of the skin, three cases of malignant mastocytosis, and in six lymph nodes with reactive intrasinusoidal increase of TMCs. Immunohistochemically, TMCs reacted positively to antisera against vimentin, common leukocyte antigen (CLA), lysozyme, alpha 1-antitrypsin (alpha 1-AT), and alpha 1-antichymotrypsin (alpha 1-ACT) and to a monoclonal antibody (KiB3) that detects preferentially B-lymphocytes. Additionally, strong positive reactions to polyclonal antisera against adrenocorticotropic hormone (ACTH) and human peptide histidine isoleucine (PHI) and weaker reactions to antisera against leu-enkephalin and met-enkephalin were observed; all other antisera tested yielded negative results. Positive stainings for vimentin, CLA, alpha 1-AT, alpha 1-ACT, and lysozyme further support the hypothesis that human TMCs may be related to the myeloid-monocytic system. The positive reactivity of TMCs to antisera against ACTH, PHI, leu-enkephalin, and met-enkephalin has not been reported previously. These findings suggest that TMCs are able to store and/or produce regulatory peptides in addition to many other well-known, granule-bound mediators.
...
PMID:Immunoreactivity of normal and neoplastic human tissue mast cells. 312 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---