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141.
Water plays an essential role in determining the structure and function of all biological systems. Recent methodological advances allow for an accurate and efficient estimation of the thermodynamic properties of water molecules at the surface of proteins. In this work, we characterize these thermodynamic properties and relate them to various structural and functional characteristics of the protein. We find that high-energy hydration sites often exist near protein motifs typically characterized as hydrophilic, such as backbone amide groups. We also find that waters around alpha helices and beta sheets tend to be less stable than waters around loops. Furthermore, we find no significant correlation between the hydration site-free energy and the solvent accessible surface area of the site. In addition, we find that the distribution of high-energy hydration sites on the protein surface can be used to identify the location of binding sites and that binding sites of druggable targets tend to have a greater density of thermodynamically unstable hydration sites. Using this information, we characterize the FKBP12 protein and show good agreement between fragment screening hit rates from NMR spectroscopy and hydration site energetics. Finally, we show that water molecules observed in crystal structures are less stable on average than bulk water as a consequence of the high degree of spatial localization, thereby resulting in a significant loss in entropy. These findings should help to better understand the characteristics of waters at the surface of proteins and are expected to lead to insights that can guide structure-based drug design efforts. 相似文献
142.
Association between polymorphisms of the CYP11A1 gene and polycystic ovary syndrome in Chinese women 总被引:1,自引:0,他引:1
Zhang CW Zhang XL Xia YJ Cao YX Wang WJ Xu P Che YN Wu XK Yi L Gao Q Wang Y 《Molecular biology reports》2012,39(8):8379-8385
The cholesterol side chain cleavage enzyme (CYP11A1) gene plays an important part in the synthesis of sex hormones and has been reported to be involved in the pathogenesis of polycystic ovary syndrome. A case-control study including 314 PCOS patients and 314 controls was conducted to assess the association of the SNPs rs4077582 and rs11632698 in CYP11A1 with PCOS using the polymerase chain reaction-restriction fragment length polymorphism method. Thereafter, 100 DNA samples were re-genotyped by direct sequencing for confirmation. The genotypic distribution of rs4077582 in women with PCOS differed from that in controls (P = 0.002). No such distributional difference was found in rs11632698 (P = 0.912). Data from our previous study of these two SNPs in another population including 290 PCOS patients and 344 controls was combined with the current data. Combined analysis (a total of 1262 participants, including 604 PCOS patients and 658 control women) showed a much more significant difference in the genotypic distribution of rs4077582 between PCOS and controls (P < 0.001). The T allele was more prevalent in PCOS patients (Odds ratio = 1.314; 95 % CI 1.122-1.540). The testosterone levels among the three genotypes for rs4077582 were different in the control group, as were the LH levels and the LH/FSH ratio. Therefore, SNP rs4077582 in CYP11A1 is strongly associated with susceptibility to PCOS and may alter the testosterone levels by the regulation of LH in different genotypes. No association was observed in rs11632698. 相似文献
143.
Lithium is the first line of therapeutic drugs used to treat both mania and depression in bipolar disorder.Although a body of research suggests that lithium acts as a cognitive enhancer, other animal studies suggest that lithium induces cognitive deficits. Comparatively, the effects of lithium on cognitive behaviour in these studies are inconsistent and contradictory. Further investigations in different species of animals and behavioural tasks are important to evaluate the possibility that lithium may act as a cognitive enhancer. In the present study, the chicks were treated intraperitoneally with lithium chloride (120 mg/kg), and the effects of chronic lithium treatment on chick cognitive behaviour were examined using a detour learning task.Additionally, the effects of chronic lithium treatment on BDNF messenger RNA (mRNA) expression were measured in RTPCR. We found that chronic lithium treatment(120 mg/kg) had no effect on spontaneous motor activity or weight gain of the chicks and that the chicks had a general healthy appearance, while chronic lithium treatment significantly promoted the response latency of detour learning and BDNF mRNA expression. These results suggest that chronic lithium treatment may improve cognitive function. 相似文献
144.
Hyperactivation of the hypothalamic–pituitary–adrenal axis and the associated hippocampal atrophy were observed in patients
with depression, which could be ameliorated by the treatment with antidepressants. Therefore, neuroprotection has been proposed
to be one of the acting mechanisms of antidepressant. Our previous studies have showed that treating mice with piperine produced
antidepressant-like effect in animal models of behavioral despair. This study aimed to examine the protective effect of piperine
treatment on corticosterone-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results showed that piperine
co-treatment revealed a differential effect on the cytotoxicity of corticosterone and had its maximum inhibitory effect at
1 μM. Piperine (1 μM) co-treatment also significantly decreased intracellular reactive oxygen species level, and enhanced
superoxide dismutase activity and total glutathione level in corticosterone-treated PC12 cells. In addition, piperine (1 μM)
co-treatment was found to reverse the decreased brain-derived neurotrophic factor (BDNF) mRNA level caused by corticosterone
in PC12 cells. The results suggest that piperine exerts a neuroprotective effect on corticosterone-induced neurotoxicity in
PC12 cells, at least in part, via the inhibition of oxidative stress and the upregulation of BDNF mRNA expression. This neuroprotective
effect may be one of the acting mechanisms accounts for the in vivo antidepressant activity of piperine. 相似文献
145.
The present study was undertaken to investigate the effect of Glomus mosseae on chlorophyll (Chl) content, Chl fluorescence parameters and chloroplast ultrastructure of beach plum seedlings under 2% NaCl stress. The results showed that compared to control, both Chl a and Chl b contents of NaCl + G. mosseae treatment were significantly lower during the salt stress, while Chl a/b ratio increased significantly. The increase of minimal fluorescence of darkadapted state (F0), and the decrease of maximal fluorescence of dark-adapted state (Fm) and variable fluorescence (Fv) values were inhibited. The maximum quantum yield of PSII photochemistry (Fv/Fm), the maximum energy transformation potential of PSII photochemistry (Fv/F0) and the effective quantum yield of PSII photochemistry (??PSII) increased significantly, especially the latter two variables. The values of the photochemical quenching coefficient (qP) and the nonphotochemical quenching (NPQ) were similar between G. mosseae inoculation and noninoculation. It could be concluded that G. mosseae inoculation could protect the photosystem II (PSII) of beach plum, enhance the efficiency of primary light energy conversion and improve the primitive response of photosynthesis under salinity stress. Meanwhile, G. mosseae inoculation was beneficial to maintain the integrity of thylakoid membrane and to protect the structure and function of chloroplast, which suggested that G. mosseae can alleviate the damage of NaCl stress to chloroplast. 相似文献
146.
Dieng H Rahman GM Abu Hassan A Che Salmah MR Satho T Miake F Boots M Sazaly A 《International journal of biometeorology》2012,56(1):113-120
Larvae of Aedes albopictus Skuse typically inhabit natural and artificial containers. Since these larval habitats are replenished by rainfall, Ae. albopictus may experience increased loss of immature stages in areas with high levels of rainfall. In this study, we investigated the
effects of rainfall and container water level on population density, and oviposition activity of Ae. albopictus. In field and laboratory experiments, we found that rainfall resulted in the flushing of breeding habitats. Excess rain negatively
impacted larval and pupal retention, especially in small habitats. When filled with water to overflowing, container habitats
were significantly repellent to ovipositing females. Taken together, these data suggest that rainfall triggers population
loss of Ae. albopictus and related species through a direct detrimental effect (flushing out) and an indirect effect (ovipositional repellency). 相似文献
147.
Leuconostoc mesenteroides subsp. mesenteroides is one of the most predominant lactic acid bacterial groups during kimchi fermentation. Here, we report the complete genome sequence of L. mesenteroides subsp. mesenteroides J18, which was isolated from kimchi. The genome of the strain consists of a 1,896,561-bp chromosome and five plasmids. 相似文献
148.
In Escherichia coli, the corA gene encodes a transporter that mediates the influx of Co(2+), Mg(2+), and Ni(2+) into the cell. During the course of experiments aimed at identifying RNase III-dependent genes in E. coli, we observed that steady-state levels of corA mRNA as well as the degree of cobalt influx into the cell were dependent on cellular concentrations of RNase III. In addition, changes in corA expression levels by different cellular concentrations of RNase III were closely correlated with degrees of resistance of E. coli cells to Co(2+) and Ni(2+). In vitro and in vivo cleavage analyses of corA mRNA identified RNase III cleavage sites in the 5'-untranslated region of the corA mRNA. The introduction of nucleotide substitutions at the identified RNase III cleavage sites abolished RNase III cleavage activity on corA mRNA and resulted in prolonged half-lives of the mRNA, which demonstrates that RNase III cleavage constitutes a rate-determining step for corA mRNA degradation. These findings reveal an RNase III-mediated regulatory pathway that functions to modulate corA expression and, in turn, the influx of metal ions transported by CorA in E. coli. 相似文献
149.
Kondo M Yoshida Y Miyata C Fujiwara S Nakajima Y Hirai H Takayama S Isogai A Che FS 《Bioscience, biotechnology, and biochemistry》2012,76(1):129-138
The immune system of plants consists of two main arms, pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity (ETI). The multiple effectors that trigger ETI are translocated into plant cells by the type III secretion system (T3SS) of pathogenic bacteria. The rice-avirulent N1141 strain of Acidovorax avenae causes ETI in rice, including hypersensitive response (HR) cell death. Sequence analysis indicated that the N1141 genome contains the hrp gene cluster (35.3 kb), including genes encoding the T3SS apparatus. The T3SS-defective N1141 mutant (NΔT3SS) did not cause HR cell death, suggesting that ETI is caused by translocation of effector proteins into rice cells via T3SS. Computational sequence analysis predicted that Lrp, HrpW, and HrpY are secreted by T3SS. The hrpY deletion mutant (NΔhrpY) did not cause ETI, suggesting that HrpY is an important effector of ETI in the interaction between A. avenae N1141 and rice. 相似文献
150.
R Feng X Zhou PM Or JY Ma XS Tan J Fu C Ma JG Shi CT Che Y Wang JH Yeung 《Phytomedicine》2012,19(12):1125-1133
Halenia elliptica D. Don is a Tibetan herb and medicinal preparations containing Halenia elliptica have been commonly used for the treatment of hepatitis B virus infection in China. The metabolism of 1-hydroxy-2,3,5-trimethoxy-xanthone (HM-1) to its metabolites is mediated through cytochrome P450 enzymes. This study aimed to investigate the herb-drug interaction potential of HM-1 by studying its effects on the metabolism of model probe substrates of five major CYP450 isoforms in human liver microsomes. HM-1 showed moderate inhibitory effects on CYP1A2 (IC(50)=1.06μM) and CYP2C9 (IC(50)=3.89μM), minimal inhibition on CYP3A4 (IC(20)=11.94μM), but no inhibition on model CYP2D6 (dextromethorphan) and CYP2E1 (chlorzoxazone) probe substrates. Inhibition kinetic studies showed that the K(i) values of HM-1 on CYP1A2, CYP2C9 and CYP3A4 were 5.12μM, 2.00μM and 95.03μM, respectively. HM-1 competitively inhibited testosterone 6β-hydroxylation (CYP3A4) but displayed mixed type inhibitions for phenacetin O-deethylation (CYP1A2) and tolbutamide 4-hydroxylation (CYP2C9). Molecular docking study confirmed the inhibition modes of HM-1 on these human CYP isoforms. 相似文献