Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proton decoupled 40.48 M Hz 31P NMR spectrum of intact and unperturbed membrane-enclosed vesicular stomatitis virus (sterotype Indiana) exhibited two distinct maxima. These can be resolved into a narrow, symmetric line and a broad asymmetric line. The 31P NMR spectrum of a multilamellar (unsonicated) preparation of the extracted viral lipids exhibited a line shape similar to that of the intact virus. A sonicated vesicle preparation of the extracted viral lipids exhibited a narrow symmetric line. The narrow component in the intact virus spectrum may be attributed to small membrane fragments. Phospholipase C digestion of the intact virus resulted in substantial reduction in intensity of both components which suggests that much of the contribution to both peaks is due to phosphate in the phospholipid polar head groups. The phospholipid phosphates in both sonicated and unsonicated preparations of the extracted viral lipids exhibited substantially longer relaxation times than did those in the intact virus. The short relaxation time emanating from the intact virus preparation is caused by immobilization of the phospholipid head groups which could be due to lipid-protein interactions. Trypsin treatment of vesicular stomatitis virions, which results in complete removal of the exterior hydrophilic segment of the membrane glycoprotein, increased the 31P relaxation time to a value similar to that observed in the protein-free total lipid extracts; this finding provides supporting evidence for the role of virus glycoprotein in shortened relaxation times. A reversible temperature-dependent change in apparent line width and absence of an effect of cholesterol on the 31P phospholipid spectrum were also demonstrated.
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PMID:The structure of vesicular stomatitis virus membrane. A phosphorus nuclear magnetic resonance approach. 18 70

Lec23 Chinese hamster ovary (CHO) cells have been shown to possess a unique lectin resistance phenotype and genotype compared with previously isolated CHO glycosylation mutants (Stanley, P., Sallustio, S., Krag, S. S., and Dunn, B. (1990) Somatic Cell Mol. Genet. 16, 211-223). In this paper, a biochemical basis for the lec23 mutation is identified. The carbohydrates associated with the G glycoprotein of vesicular stomatitis virus (VSV) grown in Lec23 cells (Lec23/VSV) were found to possess predominantly oligomannosyl carbohydrates that bound strongly to concanavalin A-Sepharose, eluted 3 sugar eq beyond a Man9GlcNAc marker oligosaccharide on ion suppression high pressure liquid chromatography, and were susceptible to digestion with jack bean alpha-mannosidase. Monosaccharide analyses revealed that the oligomannosyl carbohydrates contained glucose, indicating a defect in alpha-glucosidase activity. This was confirmed by further structural characterization of the Lec23/VSV oligomannosyl carbohydrates using purified rat mammary gland alpha-glucosidase I, jack bean alpha-mannosidase, and 1H NMR spectroscopy at 500 MHz. [3H]Glucose-labeled Glc3Man9GlcNAc was prepared from CHO/VSV labeled with [3H]galactose in the presence of the processing inhibitors castanospermine and deoxymannojirimycin. Subsequently, [3H]Glc2Man9GlcNAc was prepared by purified alpha-glucosidase I digestion of [3H]Glc3Man9GlcNAc. When these oligosaccharides were used as alpha-glucosidase substrates it was revealed that Lec23 cells are specifically defective in alpha-glucosidase I, a deficiency not previously identified among mammalian cell glycosylation mutants.
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PMID:A novel glycosylation phenotype expressed by Lec23, a Chinese hamster ovary mutant deficient in alpha-glucosidase I. 166 Apr 60

Glycoproteins synthesized by the Chinese hamster ovary cell mutants LEC11 and LEC12 carry the Lex determinant (Gal beta 1,4(Fuc alpha 1,3)GlcNAc), while those synthesized by LEC11 cells also carry the sialyl-Lex determinant (NeuAc alpha 2,3Gal beta 1,4(Fuc alpha 1,3)GlcNAc), and both mutants have been shown to possess a distinct alpha(1,3)-fucosyltransferase of the appropriate specificity to synthesize these determinants (Campbell, C., and Stanley, P. (1983) Cell 35, 303-309; Campbell, C., and Stanley, P. (1984), J. Biol. Chem. 259, 11208-11214; Howard, D. R., Fukuda, M., Fukuda, M. N., and Stanley, P. (1987) J. Biol. Chem. 262, 16830-16837). The LEC11 cells therefore provide a source of carbohydrates terminating in sialylated, fucosylated lactosamine, a relatively rare structure not previously characterized by 1H NMR spectroscopy when in association with an N-linked carbohydrate. In this paper we use a monoclonal antibody specific for Lex to show that the G glycoprotein of vesicular stomatitis virus (VSV) grown in LEC11 and LEC12 cells possesses the Lex determinant and that G from LEC11/VSV also possesses sialylated Lex. Biantennary carbohydrates purified from LEC11/VSV and LEC12/VSV were therefore used to examine the effects on the 1H NMR spectrum of the presence of alpha(1,3)-fucose residues on sialylated and unsialylated lactosamine units. Comparisons of one-dimensional spectra obtained at 500 MHz from LEC11/VSV and LEC12/VSV glycopeptides before and after neuraminidase treatment with spectra of biantennary carbohydrates lacking alpha(1,3)-fucose allowed the assignment of several new resonances. Resolution of certain signals and determinations of coupling constants were achieved by two-dimensional correlation spectroscopy (COSY) at 400 MHz and allowed the assignment of several more resonances in the one-dimensional spectrum.
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PMID:The LEC11 Chinese hamster ovary mutant synthesizes N-linked carbohydrates containing sialylated, fucosylated lactosamine units. Analysis by one- and two-dimensional 1H NMR spectroscopy. 340 33

A new antibiotic, crisamicin A, with in vitro activity against Gram-positive bacteria, B16 murine melanoma cells, and herpes simplex, vaccinia, and vesicular stomatitis viruses, has been isolated from Micromonospora purpureochromogenes subsp. halotolerans. On the basis of 1H and 13C NMR spectroscopic, high resolution field desorption mass spectrometric, and circular dichroism studies of the antibiotic and several of its derivatives, the structure of crisamicin A has been assigned.
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PMID:Isolation and structure determination of crisamicin A, a new antibiotic from Micromonospora purpureochromogenes subsp. halotolerans. 370 Feb 37

A biochemical basis for the LEC10 mutant phenotype of Chinese hamster ovary cells has been identified. Independent LEC10 mutants, originally selected for resistance to the toxicity of ricin, have been shown to exhibit reduced binding of 125I-ricin at the cell surface. Although this is indicative of structural changes in cell-surface carbohydrates, labeling of plasma membranes with galactose oxidase/[3H]borohydride revealed no significant differences between mutant and parental cells. Alterations in the carbohydrates synthesized by LEC10 cells were, however, resolved by lectin-affinity chromatography of glycopeptides from the G glycoprotein of vesicular stomatitis virus (VSV) grown in LEC10. LEC10/VSV glycopeptides contain a fraction which is not bound to concanavalin A-Sepharose but is strongly retarded on E-PHA (erythroagglutinin from Proteus vulgaris)-agarose. In contrast, CHO/VSV glycopeptides or those from a LEC 10 revertant (R.LEC 10/VSV) do not contain carbohydrates with these properties. High-field 1H NMR spectroscopy of the novel LEC10/VSV carbohydrates showed that they are complex, biantennary structures containing N-acetylglucosamine in beta(1,4)-linkage to the beta-linked core mannose residue. The presence of these structures correlates with the expression of the enzyme responsible for the addition of this "bisecting" GlcNAc residue, UDP-GlcNAc:glycopeptide beta-4-N-acetylglucosaminyltransferase III (GlcNAc-TIII). Parental Chinese hamster ovary cells and the LEC10 revertant possess no detectable GlcNAc-TIII activity. The combined evidence suggests that the LEC10 mutation induces the expression of the GlcNAc-TIII enzyme in Chinese hamster ovary cells.
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PMID:A dominant mutation to ricin resistance in Chinese hamster ovary cells induces UDP-GlcNAc:glycopeptide beta-4-N-acetylglucosaminyltransferase III activity. 623 35

Carbohydrate moieties derived from the G glycoprotein of Vesicular Stomatitis Virus (VSV) grown in parental Chinese hamster ovary (CHO) cells and the glycosylation mutant Lec4 have been analyzed by high-field 1H NMR spectroscopy. The major glycopeptides of CHO/VSV and Lec4/VSV were purified by their ability to bind to concanavalin A-Sepharose. The carbohydrates in this fraction are of the biantennary, complex type with heterogeneity in the presence of alpha(2,3)-linked sialic acid and alpha (1,6)-linked fucose residues. A minor CHO/VSV glycopeptide fraction, which does not bind to concanavalin A-Sepharose but which binds to pea lectin-agarose, was also investigated by 1H NMR spectroscopy. These carbohydrates are complex moieties which appear to contain N-acetylglucosamine in beta(1,6) linkage. Their spectral properties are most similar to those of a triantennary complex oligosaccharide containing a 2, 6-disubstituted mannose alpha (1,6) residue. Carbohydrates of this type are not found among the glycopeptides of VSV grown in the Lec4 CHO glycosylation mutant.
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PMID:1H NMR spectroscopy of carbohydrates from the G glycoprotein of vesicular stomatitis virus grown in parental and Lec4 Chinese hamster ovary cells. 632 83

We used photocross-linking of peptides to DnaK to identify elements of the peptide binding site of DnaK. We attached a photoactivatable group (N-hydroxysuccinimidyl-4-azido-salicylic acid (NHS-ASA) or N-iodoacetamidobutyl-4-azido-salicylic acid (I-ABASA)) to different positions on peptide C of the vesicular stomatitis virus glycoprotein, 125I-radiolabeled the cross-linker, cross-linked the peptide to DnaK by UV irradiation, and then determined the amino acid residues of DnaK that were cross-linked to the peptide. Limited trypsin digestion of the DnaK-peptide complex revealed that the derivatives modified with photoactivatable cross-linker peptide C cross-linked to a C-terminal fragment of DnaK and that the N-terminal 45-kDa fragment of DnaK was not cross-linked by these modified peptides. The attachment points of the three peptide C derivatives carrying photoactivatable cross-linkers at different locations on the peptide, PepC-ASA, PepC-S7C-ABASA, and PepC-S8C-ABASA, have been identified as Arg-536, Arg-527, and His-541 of DnaK, respectively. Thus all three peptides cross-linked to amino acids located close together in a sequence that includes one end of the long alpha-helix in the NMR-based secondary structure model of the peptide binding domain of Hsp70 family (Morshauser, R., Wang, H., Flynn, G., and Zuiderweg, E. (1995) Biochemistry 34, 6261-6266).
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PMID:Identification of elements of the peptide binding site of DnaK by peptide cross-linking. 870 69

The interaction of a 19 amino acid vesicular stomatitis virus G protein fragment (GTWLNPGFPPQSCGYATVT) with phosphatidylserine-containing model membranes was investigated using solution-phase 1d and 2d 1H NMR spectroscopy and intrinsic tryptophan fluorescence. Results of these studies show that this peptide interacts with model membranes containing negatively charged phospholipids. The interaction is modulated by both ionic and hydrophobic factors and appears to be dependent on the fluidity and lipid packing of the target bilayer. The data further suggest the existence of two isomeric forms of this peptide, which react differentially with model membranes. Upon binding, 2d 1H NOESY and tryptophan fluorescence data indicate penetration of the tryptophan residue into the bilayer. A model is proposed for the interaction of the peptide with model membranes, consistent with the experimental findings.
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PMID:Interactions of a vesicular stomatitis virus G protein fragment with phosphatidylserine: NMR and fluorescence studies. 985

Host-derived anti-infective proteins represent an important source of sequences for designing antimicrobial peptides (AMPs). However such sequences are often long and comprise diverse amino acids with uncertain contribution to biological effects. Previously, we identified a simple highly cationic peptide derivative of human apolipoprotein E (apoEdp) that inhibited a range of microorganisms. Here, we have dissected the protein chemistry underlying this activity. We report that basic residues and peptide length of around 18 residues were required for activity; however, the Leu residues can be substituted by several other residues without loss of activity and, when substituted with Phe or Trp, resulted in peptides with increased potency. These apoEdp-derived AMPs (apoE-AMPs) showed no cytotoxicity and minimal haemolytic activity, and were active against HIV and Plasmodium via an extracellular target. CXCR4 and CCR5 strains of HIV were inhibited though an early stage in viral infection upstream of fusion, and a lack of inhibition of vesicular stomatitis virus G protein pseudotyped HIV-1 suggested the anti-HIV activity was relatively selective. Inhibition of Plasmodium invasion of hepatocytes was observed without a direct action on Plasmodium integrity or attachment to cells. The Trp-substituted apoE-AMP adhered to mammalian cells irreversibly, explaining its increased potency; NMR experiments confirmed that the aromatic peptides also showed stronger perturbation of membrane lipids (relative to apoEdp). Our data highlight the contribution of specific amino acids to the activity of apoEdp (and also potentially unrelated AMPs) and suggest that apoE-AMPs may be useful as lead agents for preventing the early stages of HIV and Plasmodium cellular entry.
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PMID:Apolipoprotein E-derived antimicrobial peptide analogues with altered membrane affinity and increased potency and breadth of activity. 1768 Oct 18

Beyond common features in their genome organization and replication mechanisms, the evolutionary relationships among viruses of the Rhabdoviridae family are difficult to decipher because of the great variability in the amino acid sequence of their proteins. The phosphoprotein (P) of vesicular stomatitis virus (VSV) is an essential component of the RNA transcription and replication machinery; in particular, it contains binding sites for the RNA-dependent RNA polymerase and for the nucleoprotein. Here, we devised a new method for defining boundaries of structured domains from multiple disorder prediction algorithms, and we identified an autonomous folding C-terminal domain in VSV P (P(CTD)). We show that, like the C-terminal domain of rabies virus (RV) P, VSV P(CTD) binds to the viral nucleocapsid (nucleoprotein-RNA complex). We solved the three-dimensional structure of VSV P(CTD) by NMR spectroscopy and found that the topology of its polypeptide chain resembles that of RV P(CTD). The common part of both proteins could be superimposed with a backbone RMSD from mean atomic coordinates of 2.6 A. VSV P(CTD) has a shorter N-terminal helix (alpha(1)) than RV P(CTD); it lacks two alpha-helices (helices alpha(3) and alpha(6) of RV P), and the loop between strands beta(1) and beta(2) is longer than that in RV. Dynamical properties measured by NMR relaxation revealed the presence of fast motions (below the nanosecond timescale) in loop regions (amino acids 209-214) and slower conformational exchange in the N- and C-terminal helices. Characterization of a longer construct indicated that P(CTD) is preceded by a flexible linker. The results presented here support a modular organization of VSV P, with independent folded domains separated by flexible linkers, which is conserved among different genera of Rhabdoviridae and is similar to that proposed for the P proteins of the Paramyxoviridae.
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PMID:Solution structure of the C-terminal nucleoprotein-RNA binding domain of the vesicular stomatitis virus phosphoprotein. 1865 47


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