Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of methylthio-cysteine disulfide (MT-Cy) and cystamine (CAM) on the thiol production and glutathione content of a human T cell line (CEM-SS) have been investigated. MT-Cy per se and CAM in the presence of cystine greatly enhanced thiol production and glutathione content of cells while cystine alone exerted no or slight influence in the first hours. The MT-Cy- or CAM-induced extracellular SH-generation was observed both in a complete nutrient medium and even more in SH-free D-PBS. The acid-soluble thiol level and glutathione content of cells elevated markedly (up to 5-6 fold in two hours) when incubating cells in complete medium. Inhibition of glutathione synthesis by DL-buthionine (S,R)-sulfoximine did not alter the MT-Cy- or CAM-induced extracellular thiol production indicating that glutathione synthesis is not involved in this effect. The results suggest that MT-Cy easily enters the cells thus accelerating the thiol cycle in SH-poor medium while CAM promotes cystine uptake into the cells. Phenylalanine and leucine inhibited both MT-Cy- and CAM-dependent thiol production in D-PBS most effectively suggesting the involvement of the L membrane transport system in these effects.
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PMID:S-methylthio-cysteine and cystamine are potent stimulators of thiol production and glutathione synthesis. 948 18

Tyr183 is a constituent of the highly conserved YXDD motif common to all retroviral reverse transcriptases. The two aspartates in this motif are the crucial members of the catalytic carboxylate triad while residue X, which in the case of HIV-1 RT is Met184, is implicated in dNTP substrate recognition and fidelity of DNA synthesis. In an attempt to understand the function of Tyr183 in the catalytic mechanism, we generated mutants of this residue (Y183F and Y183A) and subjected them to in-depth analysis. The efficiency of reverse transcription of natural U5-PBS HIV-1 RNA template was severely impaired by both the conservative and nonconservative substitutions. The major defect identified was at the level of dNTP binding as determined by a 20-80-fold increase in the Km for the dNTP substrate on both homopolymeric and heteropolymeric RNA and DNA templates. A significant reduction in processivity of DNA synthesis by these mutants was also noted. However, the fidelity of DNA synthesis by the Y183F and Y183A mutants was increased significantly compared to the wild-type enzyme. Interestingly, the reduction in the polymerase activity due to single substitution of Tyr to Phe in the YMDD motif is compensated by a second substitution of Met to Val in the same motif, herein referred to as the FVDD. The loss of dNTP binding as well as decreased processivity of DNA synthesis exhibited by the Y183F mutant was also compensated by mutation at the second site. Curiously, the double mutant did not exhibit any synergistic effect in regard to fidelity of DNA synthesis as might be expected since both the single mutations (Y183F, M184V) exhibited enhanced fidelity compared to the wild-type enzyme. These data implicate Tyr183 and Met184 as important constituents of the dNTP-binding pocket. We propose a model which suggests that subtle structural changes due to mutation in the flexible beta9-beta10 loop region at the active site of the molecule influence the enzyme activity and substrate recognition.
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PMID:Loss of polymerase activity due to Tyr to Phe substitution in the YMDD motif of human immunodeficiency virus type-1 reverse transcriptase is compensated by Met to Val substitution within the same motif. 965 75

We previously showed that bovine apolipoprotein A-II (apoA-II) had antimicrobial activity against Escherichia coli and the yeast Saccharomyces cerevisiae in PBS. We have characterized here the active domain of apoA-II using synthetic peptides. A peptide corresponding to C-terminal residues Leu(49)-Thr(76) exhibited significant antimicrobial activity against E. coli in PBS, but not against S. cerevisiae. Experiments using amino-acid-substituted peptides indicated that the residues Phe(52)-Phe(53)-Lys(54)-Lys(55) are required for the activity. Peptide Leu(49)-Thr(76) induced the release of calcein trapped inside the vesicles whose lipid composition resembles that of E. coli membrane, suggesting that peptide Leu(49)-Thr(76) can destabilize the E. coli membrane. CD measurements showed that the alpha-helicity of peptide Leu(49)-Thr(76) increased from 3.5 to 36% by addition of the vesicles. When E. coli cells were incubated with peptide Leu(49)-Thr(76), some proteins were released to the external medium, probably owing to membrane destabilization caused by the peptide. In electron micrographs of E. coli cells treated with peptide Leu(49)-Thr(76), transparent nucleoids and granulated cytoplasm were observed. Amino acid substitutions, Phe(52)Phe(53)-->AlaAla (Phe(52, 53)-->Ala) in peptide Leu(49)-Thr(76) caused the loss of antimicrobial activity against E. coli, although protein-releasing activity was retained. Electron micrographs of the cells treated with peptide Leu(49)-Thr(76)(Phe(52,53)-->Ala) revealed morphological change only at the nucleoids. Therefore peptide Leu(49)-Thr(76) appears to primarily target the cytoplasm rather than the membrane of E. coli cells.
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PMID:Lipid-binding and antimicrobial properties of synthetic peptides of bovine apolipoprotein A-II. 1043 19

Retroviral reverse transcription is initiated from a cellular tRNA molecule and all known exogenous isolates of murine leukemia virus utilise a tRNA(Pro)molecule. While several studies suggest flexibility in murine leukemia virus primer utilisation, studies on human immunodeficiency virus and avian retro-viruses have revealed evidence of molecular adapt-ation towards the specific tRNA isoacceptor used as replication primer. In this study, murine leukemia virus tRNA utilisation is investigated by in vivo screening of a retroviral vector combinatorial library with randomised primer binding sites. While most of the selected primer binding sites are complementary to the 3'-end of tRNA((Pro)), we also retrieved PBS sequences matching four other tRNA molecules and demonstrate that Akv murine leukemia virus vectors may efficiently replicate using tRNA(Arg(CCU)), tRNA(Phe(GAA))and a hitherto unknown human tRNA(Ser(CGA)).
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PMID:Selection of functional tRNA primers and primer binding site sequences from a retroviral combinatorial library: identification of new functional tRNA primers in murine leukemia virus replication. 1063 32

Excreted/secreted products from Taenia solium metacestodes cultured in vitro were analyzed for peptidase activity using peptide substrates Z-Phe-Arg-AFC, Arg-AFC, and Z-Gly-Gly-Arg-AFC and zymography studies. Specific inhibitor profiles revealed mainly cysteine and metalloprotease activities. Hydrolysis of substrate Z-Phe-Arg-AFC was augmented by the addition of L-cysteine and acid pH, consistent with cysteine protease activity. Cysteine protease activity was more prominent in supernatants from living metacestodes cultured in PBS than in either RPMI or RPMI plus fetal calf serum and was proportional to the number of metacestodes. Flow cytometry analysis showed depletion of human T lymphocytes cultured with living T. solium metacestodes. CD4(+) expression was significantly decreased when metacestode E/S products and L-cysteine were added to lymphocyte cultures (P = 0.027). This peptidase activity was inhibited by E-64 indicating that the depletion of CD4(+) cells was due to cysteine protease activity. Thus, T. solium metacestodes produce excretory/secretory proteases. These enzymes may cleave molecules critical for the host immune response allowing the parasites to survive in the host tissues.
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PMID:Taenia solium: a cysteine protease secreted by metacestodes depletes human CD4 lymphocytes in vitro. 1083 77

A series of cycloSal-BVDUMP phosphate triesters has been prepared. The prototype compound was 3-methyl-cycloSal-BVDUMP 2. Furthermore, a series of 3'-O-acyl-modified derivatives having carboxylic acids with different lipophilicity or a L-configurated alpha-amino acid (phenylalanine) was prepared. The hydrolysis properties in phosphate buffer PBS as well as in PBS containing pig liver esterase (PLE) will be described. Finally, the biological activity against EBV has been determined.
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PMID:Synthesis, hydrolysis and anti-EBV activity of a series of 3'-modified cycloSal-BVDUMP pronucleotides. 1156 42

Barat, M. (Centre National de la Recherche Scientifique, Gif-sur-Yvette, Seine et Oise, France), C. Anagnostopoulos, and A.-M. Schneider. Linkage relationships of genes controlling isoleucine, valine, and leucine biosynthesis in Bacillus subtilis. J. Bacteriol.90:357-369. 1965.-In Bacillus subtilis, the genetic loci controlling isoleucine and valine biosynthesis are not all clustered. Some of them were located on two distinct transforming deoxyribonucleic acid "molecules." One of these molecules (the "ileilva(2-4)-met segment") carries the threonine deaminase and the dihydroxy acid dehydrase loci linked to methionine markers. The other (the "ilva(1-3)-leu segment") bears the reductoisomerase locus and one or more loci involved in leucine synthesis. A phenylalanine marker was also shown to be weakly linked to this latter group. In transduction mediated by phage PBS-1, these groups are transferred jointly with other gene clusters. The phage appears to convey chromosome fragments considerably longer than the transforming "molecules." The genetic maps of both the above segments were extended by transduction. Some groups previously studied by transformation can be placed in the following linear order: the ile-ilva(2-4)-met segment, the cluster of loci involved in aromatic amino acid synthesis (try segment), and a lysine locus. An arginine locus is cotransduced with the phe-ilva(1-2)-leu segment. Recombination frequencies between linked markers are much lower in transduction by this phage than in transformation.
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PMID:LINKAGE RELATIONSHIPS OF GENES CONTROLLING ISOLEUCINE, VALINE, AND LEUCINE BIOSYNTHESIS IN BACILLUS SUBTILIS. 1432 48

PEGylated polyamidoamine (PAMAM) dendrimers as drug carriers have been a topic of interest because of their biomedically favorable features, including minimal toxicity, reduced immunogenicity, and excellent solubility in aqueous and most organic solutions. A PEG shell on dendrimer surface may provide steric hindrance, known as stealth properties of PEG, to stabilize drug molecules to be delivered. In this article, the effects of PEG and coupling sequence of drug, PEG, and dendrimer in modulating the stability of delivered drug molecules were evaluated. N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide was chosen as a model peptide. Dendritic peptides, that is, peptide-dendrimer, peptide-PAMAM-PEG, and peptide-PEG-dendrimer, were constructed based on Starbursttrade mark G3.0 PAMAM dendrimer and characterized by (1)H-NMR spectroscopy. Hydrolysis of dendritic peptides was catalyzed by alpha-chymotrypsin in pH 7.4 PBS buffer containing 5% DMF (v/v) at room temperature. The enzymatic stability of dendritic peptides was peptide-PAMAM-PEG > peptide-PAMAM > free peptide > peptide-PEG-PAMAM. The ratio of PEG/peptide could be reduced for increasing peptide loading while maintaining the delivered peptides' relatively high enzymatic stability. The quantitative analysis of dendritic peptide/enzyme interactions provided the understandings of the molecular structure/stability relationships of dendrimer/drug for the design of an optimal PEGylated dendrimer-based drug-delivery system.
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PMID:In vitro enzymatic stability of dendritic peptides. 1627 Mar 46

Human immunodeficiency virus (HIV-1) exclusively selects tRNA(Lys,3) as the primer for initiation of reverse transcription. How and why HIV-1 selects the tRNA is unresolved. To address this issue, we have generated HIV-1 in which the PBS was changed to be complementary to alternative tRNAs. In this study, we report on HIV-1 that have the PBS mutated to be complementary to tRNA(Thr), tRNA(Phe), tRNA(Ser) and tRNA(Tyr). Virus with a PBS complementary to tRNA(Thr) grew slightly slower than the wild type virus and maintained the PBS for an extended culture period before finally reverting back to utilize tRNA(Lys,3). In contrast, viruses with a PBS complementary to tRNA(Phe) or tRNA(Ser) rapidly reverted to utilize tRNA(Lys,3) following limited in vitro replication, while a virus with a PBS complementary to tRNA(Tyr) had severely compromised infectivity and did not productively infect a continuous T cell line (SupT1) or human peripheral blood mononuclear cells (PBMC). Modification of the A-loop region to be complementary to tRNA(Thr) with the mutation in the PBS to be complementary to tRNA(Thr) resulted in a virus that could stably utilize this tRNA while the modification of the A-loop to be complementary to the anticodon of tRNA(Ser) did not allow the virus to stably utilize tRNA(Ser). Modification of the A-loop region to be complementary to the anticodon of tRNA(Phe) severely impacted the replication of this virus. Finally, the modification of the A-loop region to be complementary to tRNA(Tyr) did not rescue the virus with a PBS complementary to tRNA(Tyr). The results of these studies demonstrate the diverse effects that alteration of the PBS to force selection of alternative primers have on HIV-1 replication and provide a framework to understand the dynamics of primer selection.
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PMID:Impact of forced selection of tRNAs on HIV-1 replication and genome stability highlight preferences for selection of certain tRNAs. 1707 Sep 52

A new family of novel biodegradable poly(ether ester amide)s (PEEAs) consisting of three building blocks (L-phenylalanine, oligoethylene glycol, and aliphatic acid dichloride) were synthesized by solution polycondensation. Using N,N-dimethylacetamide as the solvent, these PEEA polymers were obtained with fairly good yields with reduced viscosity (eta(red)) ranging from 0.13 to 0.61 dL/g. The chemical structures of the PEEAs were confirmed by IR, NMR spectra, and elemental analysis. The PEEAs had Tg values lower than that of the saturated poly(ester amide)s (PEAs) of similar structures due to the incorporation of ether bonds in the backbones. An increase in the number of ether bonds in PEEA resulted in a lower Tg value. The solubility of the PEEA polymers in a wide range of common organic solvents was significantly improved when compared with unsaturated PEAs. The preliminary in vitro biodegradation behaviors of PEEA polymers were investigated in both pure PBS buffer and alpha-chymotrypsin solution of different concentrations. The polymers showed a significantly faster weight loss in an enzyme solution (alpha-chymotrypsin) but a very slow biodegradation rate in pure PBS buffer. The enzymatic hydrolysis rates of PEEAs (in terms of weight loss) were found to be much faster than those of saturated and unsaturated polyesteramides reported in previous studies. The zero-order-like biodegradation kinetics and molecular weight data also suggested surface erosion biodegradation mechanisms for these PEEAs.
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PMID:Synthesis, characterization, and biodegradation of novel poly(ether ester amide)s based on L-phenylalanine and oligoethylene glycol. 1767 2


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