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71.
Jacques Frère Abdellah Benachour Jean-Christophe Giard Jean-Marie Laplace Sigrid Flahaut Yanick Auffray 《FEMS microbiology letters》1998,161(1):107-114
We isolated a replication thermosensitive mutant of the theta-type lactococcal pUCL22 replicon. An improved version of this thermosensitive replicon was obtained by fusioning the replication repA gene with the downstream repB gene. The resulting plasmid was named pUCB3522Ts. It is highly instable at 42°C in Enterococcus faecalis. Integration into the chromosome via homologous recombination was monitored using the npr gene of E. faecalis JH2-2 as a target. A 513 bp PCR amplification product from an internal region of this npr gene was cloned into pUCB3522Ts. Integration of this construction into the JH2-2 npr gene was selected by shift temperature, from 30°C to 42°C. 85% of the analysed clones showed integration into the npr gene, demonstrating the practicality of this thermosensitive replicon as a genetic integrative tool for E. faecalis. 相似文献
72.
Yoshio Hamada Hiroko Ohta Naoko Miyamoto Diganta Sarma Takashi Hamada Tomoya Nakanishi Moe Yamasaki Abdellah Yamani Shoichi Ishiura Yoshiaki Kiso 《Bioorganic & medicinal chemistry letters》2009,19(9):2435-2439
Recently, we reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Because these inhibitors contained some natural amino acids, we would need to improve their enzymatic stability in vivo and permeability across the blood–brain barrier, so that they become practically useful. Subsequently, non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold, 2,6-pyridenedicarboxylic, chelidamic or chelidonic moiety, at the P2 position were reported. These inhibitors were designed based on the conformer of docked inhibitor in BACE1. In this study, we discuss the role and significance of interactions between Arg235 of BACE1 and its inhibitor in BACE1 inhibitory mechanism. Moreover, we designed more potent small-sized BACE1 inhibitors with a 2,6-pyridinedicarboxylic scaffold at the P2 position, that were optimized for the interactions with Arg235 of BACE1. 相似文献
73.
Abdellah Benjahad Robert Granet Pierre Krausz Claudine Bosgiraud Sylvie Delebassée 《Nucleosides, nucleotides & nucleic acids》2013,32(11-12):1849-1861
Abstract Piperazinone nucleosides can be formed by N-glycosylation with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose of either piperazin-2-ones or pyrazin-2-ones followed by reduction of the heterocycle with rhodium on alumina. All the prepared compounds were tested for their activity against the Visna virus, but did not show significant antiviral activity. 相似文献
74.
Liyan Qiu Natasha Pashkova John R. Walker Stanley Winistorfer Abdellah Allali-Hassani Masato Akutsu Robert Piper Sirano Dhe-Paganon 《The Journal of biological chemistry》2010,285(1):365-372
PLAA (ortholog of yeast Doa1/Ufd3, also know as human PLAP or phospholipase A2-activating protein) has been implicated in a variety of disparate biological processes that involve the ubiquitin system. It is linked to the maintenance of ubiquitin levels, but the mechanism by which it accomplishes this is unclear. The C-terminal PUL (PLAP, Ufd3p, and Lub1p) domain of PLAA binds p97, an AAA ATPase, which among other functions helps transfer ubiquitinated proteins to the proteasome for degradation. In yeast, loss of Doa1 is suppressed by altering p97/Cdc48 function indicating that physical interaction between PLAA and p97 is functionally important. Although the overall regions of interaction between these proteins are known, the structural basis has been unavailable. We solved the high resolution crystal structure of the p97-PLAA complex showing that the PUL domain forms a 6-mer Armadillo-containing domain. Its N-terminal extension folds back onto the inner curvature forming a deep ridge that is positively charged with residues that are phylogenetically conserved. The C terminus of p97 binds in this ridge, where the side chain of p97-Tyr805, implicated in phosphorylation-dependent regulation, is buried. Expressed in doa1Δ null cells, point mutants of the yeast ortholog Doa1 that disrupt this interaction display slightly reduced ubiquitin levels, but unlike doa1Δ null cells, showed only some of the growth phenotypes. These data suggest that the p97-PLAA interaction is important for a subset of PLAA-dependent biological processes and provides a framework to better understand the role of these complex molecules in the ubiquitin system. 相似文献
75.
Abdeladim Guermoune Al Mokhtar Lamsabhi Driss Cherqaoui Abdellah Jarid Hafid Anane Gabriel Merino 《Journal of molecular modeling》2010,16(3):551-557
The stability of the tri–μ–hydrido–bis[(η5–C5Me5)aluminum], Cp*2Al2H3, 1 is studied at B3LYP/6–311+G(d,p), CCSD(T)//B3LYP/6–311+G(d,p) and MP4//B3LYP/6–311+G(d,p) levels. The coordination between
Al2H3 entity and both C5(CH3)5 groups is ensured by strong electrostatic and orbital interactions. The orbital analysis of the interacting fragments shows
that Al2H3 acceptor, which keeps its tribridged structure, implies the vacant
( \texta1¢ ) \left( {{\text{a}}_1^\prime } \right) and five antibonding (a2¢¢ a_2^{\prime \prime } , e′ and e″) molecular orbitals to interact with two orbitals mixtures, b1 and e" of the donors (C5Me5). When we take into account the solvent effect, the computation shows that 1 seems to be stable in condensed phase with a tribridged bond between the Al atoms [Cp*Al(μ-H)3AlCp*], whereas in the gas phase, the monobridged Cp*AlH(μ-H)AlHCp* 4 is slightly favored (4 kcal mol−1). We propose that 1 could be prepared thanks to Cp*Al (2) and Cp*AlH2 (3) reaction in acidic medium. The experimental treatment of this type of metallocenes would contribute to the development of
the organometallic chemistry of 13th group elements.
相似文献
76.
Hamada Y Igawa N Ikari H Ziora Z Nguyen JT Yamani A Hidaka K Kimura T Saito K Hayashi Y Ebina M Ishiura S Kiso Y 《Bioorganic & medicinal chemistry letters》2006,16(16):4354-4359
Recently, we reported potent and small-sized beta-secretase (BACE1) inhibitors KMI-570 and KMI-684 in which we replaced carboxylic acid groups at the P(1)(') position of KMI-420 and KMI-429, respectively, with tetrazole derivatives as carboxylic acid bioisosteres. These modifications improved significantly BACE1 inhibitory activity and chemical stability. In this study, the acidic tetrazole ring of the P(4) position of KMI-420 and KMI-570, respectively, was replaced with various hydrogen bond acceptor groups. We found BACE1 inhibitor KMI-574 that exhibited potent inhibitory activity in cultured cells as well as in vitro enzymatic assay. 相似文献
77.
Rodríguez-Zavala JS Allali-Hassani A Weiner H 《Protein science : a publication of the Protein Society》2006,15(6):1387-1396
Aldehyde dehydrogenases are general detoxifying enzymes, but there are also isoenzymes that are involved in specific metabolic pathways in different organisms. Two of these enzymes are Escherichia coli lactaldehyde (ALD) and phenylacetaldehyde dehydrogenases (PAD), which participate in the metabolism of fucose and phenylalanine, respectively. These isozymes share some properties with the better characterized mammalian enzymes but have kinetic properties that are unique. It was possible to thread the sequences into the known ones for the mammalian isozymes to better understand some structural differences. Both isozymes were homotetramers, but PAD used both NAD+ and NADP+ but with a clear preference for NAD, while ALD used only NAD+. The rate-limiting step for PAD was hydride transfer as indicated by the primary isotopic effect and the absence of a pre-steady-state burst, something not previously found for tetrameric enzymes from other organisms where the rate-limiting step is related to both deacylation and coenzyme dissociation. In contrast, ALD had a pre-steady-state burst indicating that the rate-limiting step was located after the NADH formation, but the rate-limiting step was a combination of deacylation and coenzyme dissociation. Both enzymes possessed esterase activity that was stimulated by NADH; NAD+ stimulated the esterase activity of PAD but not of ALD. Finding enzymes that structurally are similar to the well-characterized mammalian enzymes but have a different rate-limiting step might serve as models to allow us to determine what regulates the rate-limiting step. 相似文献
78.
Filtration performance of microporous ceramic supports 总被引:1,自引:0,他引:1
Belouatek A Ouagued A Belhakem M Addou A 《Journal of biochemical and biophysical methods》2008,70(6):1174-1179
The use of inorganic membranes in pollution treatment is actually limited by the cost of such membranes. Advantages of inorganic membranes are their chemical, thermal and pH properties. The purpose of this work was the development of microporous ceramic materials based on clay for liquid waste processing. The supports or ceramic filters having various compositions were prepared and thermally treated at 1100 °C. The results show that, at the temperature studied, porosity varied according to the support composition from 12% for the double-layered (ceramic) support to 47% for the activated carbon- filled support with a mean pore diameter between 0.8 and 1.3 μm, respectively. Volumes of 5 l of distilled water were filtered tangentially for 3 h under an applied pressure of 3.5 and 5.5 bar. The retention of tubular supports prepared was tested with molecules of varying size (Evans blue, NaCl and Sacharose). The study of the liquid filtration and flow through these supports showed that the retention rate depends on support composition and pore diameter, and solute molecular weight. The S1 support (mixture of barbotine and 1% (w/w) activated carbon) gave a flux for distilled water of 68 L/m2 h while the double-layered support resulted in a flux of 8 L/m2 h for the same solution at the pressure of 3.5 bar. At a pressure of 5.5 bar an increase in the distilled water flux through the various supports was observed. It was significant for the S1 support (230 L/m h). 相似文献
79.
Peggy Vauchel Abdellah Arhaliass Jack Legrand Raymond Kaas Régis Baron 《Journal of phycology》2008,44(2):515-517
Alginates are natural polysaccharides that are extracted from brown seaweeds and widely used for their rheological properties. The central step in the extraction protocol used in the alginate industry is the alkaline extraction, which requires several hours. In this study, a significant decrease in alginate dynamic viscosity was observed after 2 h of alkaline treatment. Intrinsic viscosity and average molecular weight of alginates from alkaline extractions 1–4 h in duration were determined, indicating depolymerization of alginates: average molecular weight decreased significantly during the extraction, falling by a factor of 5 between 1 and 4 h of extraction. These results suggested that reducing extraction time could enable preserving the rheological properties of the extracted alginates. 相似文献
80.
Although the structures of mammalian cytosolic and mitochondrial ALDH have been determined, several differences, mainly functional, between these two 70% identical isozymes remain unexplained. A major difference is the differential effect of Mg(2+) ions that inhibits the cytosolic and activates the mitochondrial isozyme. Here, we have investigated the effect of Mg(2+) ions on each individual kinetic step of ALDH1 and ALDH2. The metal ions were found not to affect either acylation or hydride transfer for either isozyme. The lack of a Mg(2+) ion effect on hydride transfer was further demonstrated with an E399Q mutant of ALDH1 whose rate-limiting step had been changed from NADH dissociation to hydride transfer. The other steps, however, were affected by Mg(2+) ions for both isozymes. The metal ions inhibited NADH dissociation, the rate-limiting step for ALDH1, and enhanced deacylation, the rate-limiting step for ALDH2. Our results indicated that, with both isozymes, Mg(2+) ions tightened the binding of NADH, and by binding to the coenzyme, they increased the nucleophilicity of the nucleophile Cys302. The inhibition of ALDH1 and activation of ALDH2 at pH 7.4 are due to their different rate-limiting steps. Mg(2+) ions affected similarly the NADH activation of the esterase reaction for both isozymes. In contrast, the metal ions affected only the NAD(+) activation of ALDH1. This latter finding and other features described here can be rationalized on the basis of the known three-dimensional structures of the isozymes. 相似文献