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991.
992.
Fine mapping of a cis-acting sequence element in yellow fever virus RNA that is required for RNA replication and cyclization 总被引:5,自引:0,他引:5
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Corver J Lenches E Smith K Robison RA Sando T Strauss EG Strauss JH 《Journal of virology》2003,77(3):2265-2270
We present fine mapping of a cis-acting nucleotide sequence found in the 5' region of yellow fever virus genomic RNA that is required for RNA replication. There is evidence that this sequence interacts with a complementary sequence in the 3' region of the genome to cyclize the RNA. Replicons were constructed that had various deletions in the 5' region encoding the capsid protein and were tested for their ability to replicate. We found that a sequence of 18 nucleotides (residues 146 to 163 of the yellow fever virus genome, which encode amino acids 9 to 14 of the capsid protein) is essential for replication of the yellow fever virus replicon and that a slightly longer sequence of 21 nucleotides (residues 146 to 166, encoding amino acids 9 to 15) is required for full replication. This region is larger than the core sequence of 8 nucleotides conserved among all mosquito-borne flaviviruses and contains instead the entire sequence previously proposed to be involved in cyclization of yellow fever virus RNA. 相似文献
993.
NMR investigation of the catalytic mechanism of arylamine N-acetyltransferase from Salmonella typhimurium 总被引:1,自引:0,他引:1
Arylamine N-acetyltransferases (NAT) are a family of enzymes found in both eucaryotes and procaryotes, which catalyse the N-acetylation of a range of arylamine and hydrazine drugs and carcinogenic arylamines, using acetyl Coenzyme A as a cofactor. Here we describe a nuclear magnetic resonance (NMR) investigation of the interaction of substrates with Salmonella typhimurium NAT. For solution NMR investigations, pure recombinant NAT from S. typhimurium was used at up to 0.1 mM. We demonstrate that a hydrazine substrate, isoniazid (INH), binds to the protein in the absence of the cofactor, acetyl CoA, and thereby suggest that even though the catalysis may follow a ping-pong pathway, ligand-enzyme interactions can occur in the absence of acetyl CoA. 相似文献
994.
Brooke EW Davies SG Mulvaney AW Pompeo F Sim E Vickers RJ 《Bioorganic & medicinal chemistry》2003,11(7):1227-1234
Arylamine N-acetyltransferases (NATs) catalyse the acetylation of arylamine, arylhydrazine and arylhydroxylamine substrates by acetyl Coenzyme A. NAT has been discovered in a wide range of eukaryotic and prokaryotic species. Although prokaryotic NATs have been implicated in xenobiotic metabolism, to date no endogenous role has been identified for the arylamine N-acetyl transfer reaction in prokaryotes. Investigating the substrate specificity of these enzymes is one approach to determining a possible endogenous role for prokaryotic NATs. We describe an accurate and efficient assay for NAT activity that is suitable for high-throughput screening of potential NAT ligands. This assay has been utilised to identify novel substrates for pure NAT from Salmonella typhimurium and Mycobacterium smegmatis which show a relationship between the lipophilicity of the arylamine and its activity as a substrate. The lipophilic structure/activity relationship observed is proposed to depend on the topology of the active site using docking studies of the crystal structures of these NAT isoenzymes. The evidence suggests an endogenous role of NAT in the protection of bacteria from aromatic and lipophilic toxins. 相似文献
995.
996.
Deoxyhypusine synthase catalyzes the first step in hypusine (N epsilon-(4-amino-2-hydroxybutyl)lysine) synthesis in a single cellular protein, eIF5A precursor. The synthesis of deoxyhypusine catalyzed by this enzyme involves transfer of the 4-aminobutyl moiety of spermidine to a specific lysine residue in the eIF5A precursor protein to form a deoxyhypusine-containing eIF5A intermediate, eIF5A(Dhp). We recently discovered the efficient reversal of deoxyhypusine synthesis. When eIF5A([3H]Dhp), radiolabeled in the 4-aminobutyl portion of its deoxyhypusine residue, was incubated with human deoxyhypusine synthase, NAD, and 1,3-diaminopropane, [3H]spermidine was formed by a rapid transfer of the radiolabeled 4-aminobutyl side chain of the [3H]deoxyhypusine residue to 1,3-diaminopropane. No reversal was observed with [3H]hypusine protein, suggesting that hydroxylation at the 4-aminobutyl side chain of the deoxyhypusine residue prevents deoxyhypusine synthase-mediated reversal of the modification. Purified human deoxyhypusine synthase also exhibited homospermidine synthesis activity when incubated with spermidine, NAD, and putrescine. Thus it was found that [14C]putrescine can replace eIF5A precursor protein as an acceptor of the 4-aminobutyl moiety of spermidine to form radiolabeled homospermidine. The Km value for putrescine (1.12 mM) as a 4-aminobutyl acceptor, however, is much higher than that for eIF5A precursor (1.5 microM). Using [14C]putrescine as an acceptor, various spermidine analogs were evaluated as donor substrates for human deoxyhypusine synthase. Comparison of spermidine analogs as inhibitors of deoxyhypusine synthesis, as donor substrates for synthesis of deoxyhypusine (or its analog), and for synthesis of homospermidine (or its analog) provides new insights into the intricate specificity of this enzyme and versatility of the deoxyhypusine synthase reaction. 相似文献
997.
We consider an integro-differential equation for the evolution of a function f on the circle, describing an orientational aggregation process. In the first part we analyze generic bifurcations of steady-state
solutions when a single eigenvalue changes sign. Lyapunov-Schmidt reduction leads to the bifurcation equation which is solved
explicitly by formal power series. We prove that these series have positive radius of convergence. Two examples exhibit forward
and backward bifurcations, respectively. In the second part we assume that the first and second eigenvalues become positive.
Again we use Lyapunov-Schmidt reduction to arrive at the reduced bifurcation system from which we get the bifurcating branches
as power series. We calculate the two most important parameters of the reduced system for two examples; one of them has interesting
mode interactions which lead to various kinds of time-periodic solutions.
Received: 23 April 2001 / Revised version: 29 October 2002 /
Published online: 28 February 2003
Key words or phrases: Actin – Cytoskeleton – Orientational Aggregation – Bifurcation Analysis – Mode Interaction – Power Series Expansion 相似文献
998.
The controlled synthesis of biodegradable copolymers of dextran grafted with aliphatic polyesters first requires the preparation of polysaccharide derivatives soluble in organic solvents. Silylation of dextran can thus lead to such organosoluble derivatives and allows the polymerization of cyclic esters initiated from the nonsilylated OH functions. Silylation of dextran was studied in DMSO by different reactants such as 1,1,1,3,3,3-hexamethyldisilazane (HMDS) in the presence of various catalysts and N,O-bis(trimethylsilyl)acetamide (BSA). According to the silylating agent and the used experimental conditions, it was possible to obtain highly or totally silylated dextrans. In parallel, an investigation of the chemical stability of the dextran chain during silylation was performed. Thus, it was found that, when used at 50 degrees C, HMDS with or without catalysts gives a relatively high silylation yield and does not alter the dextran chain length, whereas at 80 degrees C, dextran degradation was observed. BSA is a very good silylating agent, which allows reaching 100% silylation even at 50 degrees C but provokes the degradation of the polysaccharide chains. The work was completed by a study of the reactivity order of the glucosidic OH functions toward silylation reaction. This order was found to be (OH(2) > OH(4) > OH(3)) as already reported for other reactions. 2D-NMR of highly silylated dextrans demonstrated that they are constituted of both quantitatively silylated glucose units and two types of disilylated ones. 相似文献
999.
Regeneration and restoration of the airway epithelium after mechanical, viral or bacterial injury have a determinant role in the evolution of numerous respiratory diseases such as chronic bronchitis, asthma and cystic fibrosis. The study in vivo of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to restore a functional respiratory epithelium after several weeks. Recently, human tracheal xenografts have been developed in immunodeficient severe combined immunodeficiency (SCID) and nude mice. In this review we recall that human airway cells implanted in such conditioned host grafts can regenerate a well-differentiated and functional human epithelium; we stress the interest in these humanized mice in assaying candidate progenitor and stem cells of the human airway mucosa. 相似文献
1000.
The influence of monovalent cations on DNA conformation and readout is an open question. This NMR study of DNA with either Na(+) or K(+) at physiological concentrations shows that the nature of the cation affects the (31)P chemical shifts (deltaP) and the sequential distances H2'(i)-H6/8(i+1), H2"(i)-H6/8(i+1), and H6/8(i)-H6/8(i+1). The deltaP and distance variations ascertain that the nature of the cation affects the DNA overall structure, i.e. both the conformational equilibria between the backbone BI (epsilon-zeta <0 degrees ) and BII (epsilon-zeta >0 degrees ) states and the helical parameters, via their strong mechanical coupling. These results reveal that Na(+) and K(+) interactions with DNA are different and sequence-dependent. These ions modulate the overall intrinsic properties of DNA, and possibly its packaging and readout. 相似文献