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101.
Summary Studies with the atypical muscarinic antagonist pirenzepine provide convincing evidence for the classification of muscarinic acetylcholine receptors (mAChRs) into two subtypes, M1 and M2. The present study examines the heterogeneity of the M2 subtype employing the newly developed competitive muscarinic antagonist, AFDX-116. Comparison of the binding affinities of pirenzepine, atropine, and AFDX-116 to mAChRs in microsomes from the rabbit cerebral cortex, heart, and iris smooth muscle shows that iris mAChRs, which are pharmacologically of the M2 subtype, can be distinguished from M2 cardiac receptors based on their affinity for AFDX-116. These results are consistent with the hypothesis that the M2 receptor subtype consists of a heterogeneous population of receptors.Abbreviations mAChRs
Muscarinic Acetylcholine Receptors
- CCh
Carbachol
- NMS
N-Methylscopolamine
- AFDX-116
11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6Hpyrido[2,3-b][1,4]benzodiazepine-6-one 相似文献
102.
Griko NB Rose-Young L Zhang X Carpenter L Candas M Ibrahim MA Junker M Bulla LA 《Biochemistry》2007,46(35):10001-10007
The Cry1Ab toxin produced by Bacillus thuringiensis (Bt) exerts insecticidal action upon binding to BT-R1, a cadherin receptor localized in the midgut epithelium of the tobacco hornworm Manduca sexta [Dorsch, J. A., Candas, M., Griko, N. B., Maaty, W. S., Midboe, E. G., Vadlamudi, R. K., and Bulla, L. A., Jr. (2002) Cry1A toxins of Bacillus thuringiensis bind specifically to a region adjacent to the membrane-proximal extracellular domain of BT-R1 in Manduca sexta: involvement of a cadherin in the entomopathogenicity of Bacillus thuringiensis, Insect Biochem. Mol. Biol. 32, 1025-1036]. BT-R1 represents a family of invertebrate cadherins whose ectodomains (ECs) are composed of multiple cadherin repeats (EC1 through EC12). In the present work, we determined the Cry1Ab toxin binding site in BT-R1 in the context of cadherin structural determinants. Our studies revealed a conserved structural motif for toxin binding that includes two distinct regions within the N- and C-termini of EC12. These regions are characterized by unique sequence signatures that mark the toxin-binding function in BT-R1 as well as in homologous lepidopteran cadherins. Structure modeling of EC12 discloses the conserved motif as a single broad interface that holds the N- and C-termini in close proximity. Binding of toxin to BT-R1, which is univalent, and the subsequent downstream molecular events responsible for cell death depend on the conserved motif in EC12. 相似文献
103.
Moustafa I Connaris H Taylor M Zaitsev V Wilson JC Kiefel MJ von Itzstein M Taylor G 《The Journal of biological chemistry》2004,279(39):40819-40826
Vibrio cholerae neuraminidase (VCNA) plays a significant role in the pathogenesis of cholera by removing sialic acid from higher order gangliosides to unmask GM1, the receptor for cholera toxin. We previously showed that the structure of VCNA is composed of a central beta-propeller catalytic domain flanked by two lectin-like domains; however the nature of the carbohydrates recognized by these lectin domains has remained unknown. We present here structures of the enzyme in complex with two substrates, alpha-2,3-sialyllactose and alpha-2,6-sialyllactose. Both substrate complexes reveal the alpha-anomer of N-acetylneuraminic acid (Neu5Ac) bound to the N-terminal lectin domain, thereby revealing the role of this domain. The large number of interactions suggest a relatively high binding affinity for sialic acid, which was confirmed by calorimetry, which gave a Kd approximately 30 microm. Saturation transfer difference NMR using a non-hydrolyzable substrate, Neu5,9Ac2-2-S-(alpha-2,6)-GlcNAcbeta1Me, was also used to map the ligand interactions at the VCNA lectin binding site. It is well known that VCNA can hydrolyze both alpha-2,3- and alpha-2,6-linked sialic acid substrates. In this study using alpha-2,3-sialyllactose co-crystallized with VCNA it was revealed that the inhibitor 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en) was bound at the catalytic site. This observation supports the notion that VCNA can produce its own inhibitor and has been further confirmed by 1H NMR analysis. The discovery of the sialic acid binding site in the N-lectin-like domain suggests that this might help target VCNA to sialic acid-rich environments, thereby enhancing the catalytic efficiency of the enzyme. 相似文献
104.
Regulation,sensory domains and roles of two Desulfovibrio desulfuricans ATCC27774 Crp family transcription factors,HcpR1 and HcpR2, in response to nitrosative stress 下载免费PDF全文
105.
Alkaliphilic actinomycetes isolated from sediment samples of the Izmir Gulf, Turkey were studied for the production of protease activity. Strain MA1-1 was selected as a good alkaline protease producer as measured by the clear zone diameter by the hydrolysis of skim-milk and casein. The alkaline protease production from the marine alkaliphilic actinomycete MA1-1 was studied by using different carbon and nitrogen sources in medium containing glycerol, peptone, KCl, MgSO4, K2HPO4, and trace elements at 30°C for 72 h. Among the different carbon and nitrogen sources, fructose, starch, maltose, D(+) glucose, yeast extract, malt extract, beef extract and peptone provided higher production of protease. Starch was also found to be effective for growth and enzyme production with highest specific activity at 699 U mg?1. Purification was achieved by adsorption on Diaion HP 20 which resulted in a recovery rate of 68% with a specific activity of 7618 U mg?1 protein and 40-fold purification. The optimum pH and temperature of the partially purified protease were determined as pH 9.0 and 50°C, but high activity was also observed at pH 8.0–13.0 and 35–50°C. The inhibition profile exhibited by phenylmethylsulphonyl fluoride (PMSF) showed that this enzyme belongs to the serine-protease group. 相似文献
106.
Y chromosome lineage- and village-specific genes on chromosomes 1p22 and 6q27 control visceral leishmaniasis in Sudan 下载免费PDF全文
Miller EN Fadl M Mohamed HS Elzein A Jamieson SE Cordell HJ Peacock CS Fakiola M Raju M Khalil EA Elhassan A Musa AM Ibrahim ME Blackwell JM 《PLoS genetics》2007,3(5):e71
Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishmania donovani is under genetic control. A recent genome scan provided evidence for a major susceptibility gene on Chromosome 22q12 in the Aringa ethnic group in Sudan. We now report a genome-wide scan using 69 families with 173 affected relatives from two villages occupied by the related Masalit ethnic group. A primary ten-centimorgan scan followed by refined mapping provided evidence for major loci at 1p22 (LOD score 5.65; nominal p = 1.72 × 10−7; empirical p < 1 × 10−5; λS = 5.1) and 6q27 (LOD score 3.74; nominal p = 1.68 × 10−5; empirical p < 1 × 10−4; λS = 2.3) that were Y chromosome–lineage and village-specific. Neither village supported a visceral leishmaniasis susceptibility gene on 22q12. The results suggest strong lineage-specific genes due to founder effect and consanguinity in these recently immigrant populations. These chance events in ethnically uniform African populations provide a powerful resource in the search for genes and mechanisms that regulate this complex disease. 相似文献
107.
Twenty-five strains of Lactococcus lactis subspecies lactis and subspecies cremoris obtained from dairy industry and environmental collections were examined by 16S RNA automated ribotyping profiles and site-specific
PCR (S-PCR). By automated ribotyping, the majority of strains were classified in accordance with phenotypic characterization,
with the exception of one lactis (220) and two cremoris (BO32 and 140) strains. A complete differentiation of subspecies lactis and cremoris in agreement with conventional phenotypic methods was achieved by S-PCR with a set of site-specific primer pairs (PR1, RM4,
and F3) designed particularly from a deletion region found in subspecies cremoris, but not in lactis. Therefore, S-PCR with primers (PR1, RM4, and F3) is a rapid and very sensitive method for the distinction of lactis and cremoris subspecies in dairy production.
Received: 19 June 2000 / Accepted: 17 July 2000 相似文献
108.
A weathered medium crude oil was applied to experimental plots of Scirpus pungens (Three-square Bulrush) in a freshwater wetland to determine the efficacy of strategies for shoreline oil spill bioremediation based on nutrient enrichment (bioremediation) and plant growth (phytoremediation). Plots were unoiled, oiled with no added nutrients, or oiled with repeated applications of phosphate and nitrate fertilizers. Following initial treatments, the experimental plots were raked to simulate the activity of wave action on oil penetration, and plants in one fertilized plot were cut repeatedly. The sediments were sampled at regular intervals for 15 months after oiling, and the loss of oil was assessed by 4-day laboratory tests of polynuclear aromatic hydrocarbon (PAH) bioaccumulation by trout, as demonstrated by increases in activity of liver cytochrome P450 (CYP1A) enzymes. Oil alone, oil mixed with sediments in the lab, and oiled sediments from treated plots all induced CYP1A activity relative to untreated controls, indicating the presence and bioavailability of PAH. Induction did not vary with nutrient treatments, but declined by 80% within 15 months of oiling, and chemical analyses indicated equivalent losses of hydrocarbons in sediment. These results demonstrate that bioavailable PAHs persisted in measurable quantities for at least 1.25 years following oiling, and that stimulation of plant growth did not affect the rate of oil disappearance. The controlling factors were likely weathering and sediment movement. 相似文献
109.
Ibrahim A. Al-Suwaidan Alaa A.-M. Abdel-Aziz Taghreed Z. Shawer Rezk R. Ayyad Amer M. Alanazi Ahmad M. El-Morsy 《Journal of enzyme inhibition and medicinal chemistry》2016,31(1):78-89
A novel series of 3-benzyl-substituted-4(3H)-quinazolinones were designed, synthesized and evaluated for their in vitro antitumor activity. The results of this study demonstrated that 2-(3-benzyl-6-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)acetamide, 2-(3-benzyl-6,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)acetamide and 3-(3-benzyl-6-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)-propanamide have shown amazing broad spectrum antitumor activity with mean GI50 (10.47, 7.24 and 14.12?µM. respectively), and are nearly 1.5–3.0-fold more potent compared with the positive control 5-FU with mean GI50, 22.60?µM. On the other hand, compounds 6 and 10 yielded selective activities toward CNS, renal and breast cancer cell lines, whereas compound 9 showed selective activities towards leukemia cell lines. Molecular docking methodology was performed for compounds 7 and 8 into ATP binding site of EGFR-TK which showed similar binding mode to erlotinib, while compound 11 into ATP binding site of B-RAF kinase inhibited the growth of melanoma cell lines through inhibition of B-RAF kinase, similar to PLX4032. 相似文献