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121.
Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity 总被引:3,自引:0,他引:3
122.
Tomasz Korzeniak Corine Mathonière Abdellah Kaiba Philippe Guionneau Marcin Koziel Barbara Sieklucka 《Inorganica chimica acta》2008,361(12-13):3500-3504
Ionic triads formed by [NiII(bipy)3]2+ (bipy = 2,2′-bipyridyl) and diamagnetic [MIV(CN)8]4? (M = Mo and W) were prepared and structurally characterized. The two compounds are isostructural and their structure consists of a three-dimensional hydrogen-bonded framework where cation–anion interactions occur through short contacts M–CN?H–C(bipy). Before irradiation, the Mo analogue behaves as paramagnet with small intermolecular interactions between the [NiII(bipy)3]2+ cations. Upon irradiation with visible light, it exhibits a reversible photomagnetic effect, which is interpreted in terms of the formation of paramagnetic [MoV(CN)8]3? and [NiII(bipy)2(bipy?)]+ due to the outer-sphere electron transfer. 相似文献
123.
Complete genome sequence of uropathogenic Proteus mirabilis, a master of both adherence and motility 总被引:1,自引:0,他引:1
Pearson MM Sebaihia M Churcher C Quail MA Seshasayee AS Luscombe NM Abdellah Z Arrosmith C Atkin B Chillingworth T Hauser H Jagels K Moule S Mungall K Norbertczak H Rabbinowitsch E Walker D Whithead S Thomson NR Rather PN Parkhill J Mobley HL 《Journal of bacteriology》2008,190(11):4027-4037
The gram-negative enteric bacterium Proteus mirabilis is a frequent cause of urinary tract infections in individuals with long-term indwelling catheters or with complicated urinary tracts (e.g., due to spinal cord injury or anatomic abnormality). P. mirabilis bacteriuria may lead to acute pyelonephritis, fever, and bacteremia. Most notoriously, this pathogen uses urease to catalyze the formation of kidney and bladder stones or to encrust or obstruct indwelling urinary catheters. Here we report the complete genome sequence of P. mirabilis HI4320, a representative strain cultured in our laboratory from the urine of a nursing home patient with a long-term (> or =30 days) indwelling urinary catheter. The genome is 4.063 Mb long and has a G+C content of 38.88%. There is a single plasmid consisting of 36,289 nucleotides. Annotation of the genome identified 3,685 coding sequences and seven rRNA loci. Analysis of the sequence confirmed the presence of previously identified virulence determinants, as well as a contiguous 54-kb flagellar regulon and 17 types of fimbriae. Genes encoding a potential type III secretion system were identified on a low-G+C-content genomic island containing 24 intact genes that appear to encode all components necessary to assemble a type III secretion system needle complex. In addition, the P. mirabilis HI4320 genome possesses four tandem copies of the zapE metalloprotease gene, genes encoding six putative autotransporters, an extension of the atf fimbrial operon to six genes, including an mrpJ homolog, and genes encoding at least five iron uptake mechanisms, two potential type IV secretion systems, and 16 two-component regulators. 相似文献
124.
Matthieu Chabannes Abdellah Barakate Catherine Lapierre Jane M. Marita John Ralph Michel Pean Saïda Danoun Claire Halpin Jacqueline Grima-Pettenati Alain Michel Boudet 《The Plant journal : for cell and molecular biology》2001,28(3):257-270
Different transgenic tobacco lines down-regulated for either one or two enzymes of the monolignol pathway were compared for their lignin content and composition, and developmental patterns. The comparison concerned CCR and CAD down-regulated lines (homozygous or heterozygous for the transgene) and the hybrids resulting from the crossing of transgenic lines individually altered for CCR or CAD activities. Surprisingly, the crosses containing only one allele of each antisense transgene, exhibit a dramatic reduction of lignin content similar to the CCR down-regulated parent but, in contrast to this transgenic line, display a normal phenotype and only slight alterations of the shape of the vessels. Qualitatively the lignin of the double transformant displays characteristics more like the wild type control than either of the other transgenics. In the transgenics with a low lignin content, the transformations induced other biochemical changes involving polysaccharides, phenolic components of the cell wall and also soluble phenolics. These results show that the ectopic expression of a specific transgene may have a different impact depending on the genetic background and suggest that the two transgenes present in the crosses may operate synergistically to reduce the lignin content. In addition, these data confirm that plants with a severe reduction in lignin content may undergo normal development at least in controlled conditions. 相似文献
125.
Vendeville S Nilsson M de Kock H Lin TI Antonov D Classon B Ayesa S Ivanov V Johansson PO Kahnberg P Eneroth A Wikstrom K Vrang L Edlund M Lindström S Van de Vreken W McGowan D Tahri A Hu L Lenz O Delouvroy F Van Dooren M Kindermans N Surleraux D Wigerinck P Rosenquist A Samuelsson B Simmen K Raboisson P 《Bioorganic & medicinal chemistry letters》2008,18(23):6189-6193
A novel series of P3-truncated macrocyclic HCV NS3/4A protease inhibitors containing a P2 proline-urea or carbamate scaffold was synthesized. Very potent inhibitors were obtained through the optimization of the macrocycle size, urea and proline substitution, and bioisosteric replacement of the P1 carboxylic acid moiety. Variation of the lipophilicity by introduction of small lipophilic substituents resulted in improved PK profiles, ultimately leading to compound 13Bh, an extremely potent (K(i)=0.1 nM, EC(50)=4.5 nM) and selective (CC(50) (Huh-7 cells)>50 microM) inhibitor, displaying an excellent PK profile in rats characterized by an oral bioavailability of 54% and a high liver exposure after oral administration. 相似文献
126.
Hamada Y Abdel-Rahman H Yamani A Nguyen JT Stochaj M Hidaka K Kimura T Hayashi Y Saito K Ishiura S Kiso Y 《Bioorganic & medicinal chemistry letters》2008,18(5):1649-1653
Recently, we reported potent BACE1 inhibitors KMI-429, -684, and -574 possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. These inhibitors showed potent inhibitory activities in enzymatic and cell assays, especially, KMI-429 was confirmed to significantly inhibit Abeta production in vivo. However, acidic moieties at the P(4) and P(1)' positions of KMI-compounds were thought to be unfavorable for membrane permeability across the blood-brain barrier. Herein, we replaced acidic moieties at the P(4) position with other hydrogen bond acceptor groups, and these inhibitors exhibited improved BACE1 inhibitory activities in cultured cells. In this study, we replaced the acidic moieties at the P(1)' position with non-acidic and low molecular sized moieties. 相似文献
127.
Hamada Y Ohta H Miyamoto N Yamaguchi R Yamani A Hidaka K Kimura T Saito K Hayashi Y Ishiura S Kiso Y 《Bioorganic & medicinal chemistry letters》2008,18(5):1643-1647
Recently, we reported substrate-based beta-secretase (BACE1) inhibitors with a hydroxymethylcarbonyl (HMC) isostere as a substrate transition-state mimic. These inhibitors showed potent BACE1 inhibitory activities (approximately 1.2 nM IC(50)). In order to improve in vivo enzymatic stability and permeability across the blood-brain barrier, these penta-peptidic inhibitors would need to be further optimized. On the other hand, non-peptidic inhibitors possessing isophthalic residue at the P(2) position were reported from other research groups. We selected isophthalic-type aromatic residues at the P(2) position and an HMC isostere at the P(1) position as lead compounds. On the basis of the design approach focused on the conformer of docked inhibitor in BACE1, we found novel non-peptidic and small-sized BACE1 inhibitors possessing a 2,6-pyridinedicarboxylic, chelidamic or chelidonic residue at the P(2) position. 相似文献
128.
Control of P-glycoprotein activity by membrane cholesterol amounts and their relation to multidrug resistance in human CEM leukemia cells 总被引:6,自引:0,他引:6
Gayet L Dayan G Barakat S Labialle S Michaud M Cogne S Mazane A Coleman AW Rigal D Baggetto LG 《Biochemistry》2005,44(11):4499-4509
P-glycoprotein (P-gp) is the most well-known ATP-binding cassette (ABC) transporter involved in unidirectional substrate translocation across the membrane lipid bilayer, thereby causing the typical multidrug resistance (MDR) phenotype expressed in many cancers. We observed that in human CEM acute lymphoblastic leukemia cells expressing various degrees of chemoresistance and where P-gp was the sole MDR-related ABC transporter detected, the amount of esterified cholesterol increased linearly with the level of resistance to vinblastine while the amounts of total and free cholesterol increased in a nonlinear way. Membrane cholesterol controlled the ATPase activity of P-gp in a linear manner, whereas the P-gp-induced daunomycin efflux decreased nonlinearly with the depletion of membrane cholesterol. All these elements suggest that cholesterol controls both the ATPase and the drug efflux activities of P-gp. In addition, in CEM cell lines that expressed increasing levels of elevated chemoresistance, the amount of P-gp increases to a plateau value of 40% of the total membrane proteins and remained unvaried while the amount of membrane cholesterol increased with the elevation of the MDR level, strongly suggesting that cholesterol may be directly involved in the typical MDR phenotype. Finally, we showed that the decreased daunomycin efflux by P-gp due to the partial depletion of membrane cholesterol was responsible for the efficient chemosensitization of resistant CEM cells, which could be totally reversed after cholesterol repletion. 相似文献
129.
The Lactobacillus casei ptsHI47T mutation causes overexpression of a LevR-regulated but RpoN-independent operon encoding a mannose class phosphotransferase system
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Mazé A Boël G Poncet S Mijakovic I Le Breton Y Benachour A Monedero V Deutscher J Hartke A 《Journal of bacteriology》2004,186(14):4543-4555
130.
Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins involved in neuronal differentiation and axonal guidance. CRMP2 was previously shown to mediate the repulsive effect of Sema3A on axons and to participate in axonal specification. The X-ray crystal structure of murine CRMP1 was determined at 2.1 A resolution and demonstrates that CRMP1 is a bilobed 'lung-shaped' protein forming a tetrameric assembly. Structure-based mutagenesis of surface-exposed residues was employed to map functional domains. As a rapid assay for CRMP, we exploited a reconstituted Sema3A signaling system in COS-7 cells expressing the receptor components Neuropilin1 and PlexinA1 (NP1/PlexA1). In these cells, CRMP and PlexA1 form a physical complex that is reduced in amount by NP1 but enhanced by Sema3A/NP1. Furthermore, CRMP accelerates Sema3A-induced cell contraction. Alanine substitutions in one domain of CRMP1 produce a constitutively active protein that causes Sema3A-independent COS-7 contraction. This mutant CRMP mimics the DRG neurite outgrowth-inhibiting effects of Sema3A and reduces Sema3A-induced axonal repulsion. These data provide a structural view of CRMP function in Plex-dependent Sema3A signaling. 相似文献