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81.
Beranič N Brožič P Brus B Sosič I Gobec S Lanišnik Rižner T 《The Journal of steroid biochemistry and molecular biology》2012,130(1-2):16-25
The human aldo-keto reductase AKR1C2 converts 5α-dihydrotestosterone to the less active 3α-androstanediol and has a minor 20-ketosteroid reductase activity that metabolises progesterone to 20α-hydroxyprogesterone. AKR1C2 is expressed in different peripheral tissues, but its role in uterine diseases like endometriosis has not been studied in detail. Some progestins used for treatment of endometriosis inhibit AKR1C1 and AKR1C3, with unknown effects on AKR1C2. In this study we investigated expression of AKR1C2 in the model cell lines of peritoneal endometriosis, and examined the ability of recombinant AKR1C2 to metabolise progesterone and progestin dydrogesterone, as well as its potential inhibition by progestins. AKR1C2 is expressed in epithelial and stromal endometriotic cell lines at the mRNA level. The recombinant enzyme catalyses reduction of progesterone to 20α-hydroxyprogesterone with a 10-fold lower catalytic efficiency than the major 20-ketosteroid reductase, AKR1C1. AKR1C2 also metabolises progestin dydrogesterone to its 20α-dihydrodydrogesterone, with 8.6-fold higher catalytic efficiency than 5α-dihydrotestosterone. Among the progestins that are currently used for treatment of endometriosis, dydrogesterone, medroxyprogesterone acetate and 20α-dihydrodydrogesterone act as AKR1C2 inhibitors with low μM K(i) values in vitro. Their potential in vivo effects should be further studied. 相似文献
82.
The maximum chlorophyll fluorescence lifetime in isolated photosystem II (PSII) light-harvesting complex (LHCII) antenna is 4 ns; however, it is quenched to 2 ns in intact thylakoid membranes when PSII reaction centers (RCIIs) are closed (Fm). It has been proposed that the closed state of RCIIs is responsible for the quenching. We investigated this proposal using a new, to our knowledge, model system in which the concentration of RCIIs was highly reduced within the thylakoid membrane. The system was developed in Arabidopsis thaliana plants under long-term treatment with lincomycin, a chloroplast protein synthesis inhibitor. The treatment led to 1), a decreased concentration of RCIIs to 10% of the control level and, interestingly, an increased antenna component; 2), an average reduction in the yield of photochemistry to 0.2; and 3), an increased nonphotochemical chlorophyll fluorescence quenching (NPQ). Despite these changes, the average fluorescence lifetimes measured in Fm and Fm' (with NPQ) states were nearly identical to those obtained from the control. A 77 K fluorescence spectrum analysis of treated PSII membranes showed the typical features of preaggregation of LHCII, indicating that the state of LHCII antenna in the dark-adapted photosynthetic membrane is sufficient to determine the 2 ns Fm lifetime. Therefore, we conclude that the closed RCs do not cause quenching of excitation in the PSII antenna, and play no role in the formation of NPQ. 相似文献
83.
Free and glucosidic bound leaf volatiles of Degenia velebitica were isolated and fractionated simultaneously into H2O‐soluble, H2O‐insoluble, and highly volatile compounds by hydrodistillation–adsorption (HDA) and analyzed by GC/MS. Among the 24 constituents identified, the main compounds obtained by the HDA method were S‐ and/or N‐atom containing compounds, i.e., 6‐(methylsulfanyl)hexanenitrile ( 10 ; 26.78%), dimethyl trisulfide ( 6 ; 26.35%), 3,4,5‐trimethylpyrazole ( 17 ; 13.33%), hex‐5‐enenitrile ( 2 ; 10.11%), dimethyl tetrasulfide ( 8 ; 4.93%), and pent‐4‐enyl isothiocyanate ( 7 ; 4.45%). In addition, O‐glycosidically bound volatiles and free volatiles were isolated by solvent extraction. Sixteen volatile O‐aglycones and twelve free volatile components were identified. The main O‐aglycones were eugenol ( 19 ; 24.15%), 2‐methoxy‐4‐vinylphenol ( 11 ; 11.50%), and benzyl alcohol ( 20 ; 9.49%), and the main free volatiles were (9Z,12Z)‐octa‐9,12‐dienic acid (38.35%), hexadecanoic acid (22.64%), and phytol (5.80%). The H2O‐soluble volatile fraction obtained by HDA, containing mostly glucosinolate degradation products and 3,4,5‐trimethylpyrazole ( 17 ), was evaluated for antimicrobial activity by determining inhibition zones with the diffusion method as well as minimal inhibitory concentrations (MIC) and minimal microbicidal concentrations (MMC) with the micro‐dilution method. The fraction expressed activity against the tested Gram‐positive and Gram‐negative bacteria as well as against yeast, with MIC values equal to or lower than 16.7 μg/ml. 相似文献
84.
85.
Bártová I Otyepka M Kríz Z Koca J 《Protein science : a publication of the Protein Society》2004,13(6):1449-1457
Nanoseconds long molecular dynamics (MD) trajectories of differently active complexes of human cyclin-dependent kinase 2 (inactive CDK2/ATP, semiactive CDK2/Cyclin A/ATP, fully active pT160-CDK2/Cyclin A/ATP, inhibited pT14-; pY15-; and pT14,pY15,pT160-CDK2/Cyclin A/ATP) were compared. The MD simulations results of CDK2 inhibition by phosphorylation at T14 and/or Y15 sites provide insight into the structural aspects of CDK2 deactivation. The inhibitory sites are localized in the glycine-rich loop (G-loop) positioned opposite the activation T-loop. Phosphorylation of T14 and both inhibitory sites T14 and Y15 together causes ATP misalignment for phosphorylation and G-loop conformational change. This conformational change leads to the opening of the CDK2 substrate binding box. The phosphorylated Y15 residue negatively affects substrate binding or its correct alignment for ATP terminal phospho-group transfer to the CDK2 substrate. The MD simulations of the CDK2 activation process provide results in agreement with previous X-ray data. 相似文献
86.
Dagmar Jičínská Eduard Brabec Marcel Rejmánek Jan Jeník Joří Haager Josef Holub Věroslav Samek Hana Rambousková Josef Holub Marie Naděžda Končalová Robert Neuhäusl Josev Kyncl František Krahuleo Jaroslav Dobrý Blanka Úlehlová Jiří Úlehla Eliška Rybníčková Kamil Rybníček 《Folia Geobotanica》1982,17(4):431-448
87.
Influence of the acetylcholinesterase active site protonation on omega loop and active site dynamics
Wiesner J Kříž Z Kuča K Jun D Koča J 《Journal of biomolecular structure & dynamics》2010,28(3):393-403
Existence of alternative entrances in acetylcholinesterase (AChE) could explain the contrast between the very high AChE catalytic efficiency and the narrow and long access path to the active site revealed by X-ray crystallography. Alternative entrances could facilitate diffusion of the reaction products or at least water and ions from the active site. Previous molecular dynamics simulations identified side door and back door as the most probable alternative entrances. The simulations of non-inhibited AChE suggested that the back door opening events occur only rarely (0.8% of the time in the 10ns trajectory). Here we present a molecular dynamics simulation of non-inhibited AChE, where the back door opening appears much more often (14% of the time in the 12ns trajectory) and where the side door opening was observed quite frequently (78% of trajectory time). We also present molecular dynamics, where the back door does not open at all, or where large conformational changes of the AChE omega loop occur together with alternative passage opening events. All these differences in AChE dynamical behavior are caused by different protonation states of two glutamate residues located on bottom of the active site gorge (Glu202 and G450 in Mus musculus AChE). Our results confirm the results of previous molecular dynamics simulations, expand the view and suggest the probable reasons for the overall conformational behavior of AChE omega loop. 相似文献
88.
RCH-microscopy (Relief Contrast after Hostounsky) is a new method of optical microscopy in transmitted light developed withLambda Ltd., Prague. This method was used to study bacteria, fungi including yeasts and algae at high magnification. The equipment provides
a three-dimensional image of high contrast and resolution. The results of these microscopic observations can be used for both
morphological (taxonomical) and ecological studies of microorganisms. 相似文献
89.
This paper illustrates the potential of the sol-gel process to imprint the pharmaceutical active--N-[N-[(1S)-1-carboxssy-3-phenylpropyl]-l-lysyl]-L-proline, (lisinopril dihydrate). This template exhibits unique difficulties such as limited solubility in non-polar and most polar porogens with multiple functionality evident in its 4 pKa values. Selectivity for this template was achieved using a 3-monomer sol-gel system utilising solid phase extraction (SPE). Analysis of the template and its related substances was achieved using HPLC. The effect of solvent polarity on the rebinding of the template was studied. Through optimisation of porogen and extraction solvent, the imprinted material (MIP) demonstrated enhanced selectivity, for the template, over a non-imprinted material (NIP). Selectivity was also illustrated for the original template over two of its related substances. The effect of starting monomer ratio on selectivity was studied to determine the interactions, which could best be exploited to further enhance selectivity. 相似文献
90.
Conclusions From our experiments it could be seen that a quite definite relationship exists between various dermatophytes and the soil which is expressed on the one side by antagonistic action of the microflora in the soil inhibiting the growth of dermatophytes and on the other, by ability of some dermatophytes to persist in the soil or to use the soil as habitat in their saprophytic life. This condition appears to be the reflection of the evolutive tendency of dermatophytes to develop from its primary habitat, the soil, to the parasitic life on man and animal. It is persumed that this evolution of dermatophytes is based on mutations of gens as one of the fundamental phenomenons in nature. It is obvious that this evolution of dermatophytes is not completed. Our experiments regardingT. mentagrophytes indicate that this species is at present still to a certain extent in a transitional evolutive stage with retained but limited ability to the life in the soil and with an evident tendency for adaption on small rodents and human beings. In this course of development on a lower level isK. ajelloi andM. gypseum with full ability of saprophytic life in the soil and with slowly but increasing pathogenicity for men and animals.
E. I. Grin, Prof. of Dermatology, Med. Faculty, Univ. Sarajevo, Director Institute of Dermatovenerology.
L. Oegovi, Prof. of Intern. Dis., Veter. Faculty, Univ. Sarajevo, Chief of Dept. of Mycology Inst. of Dermatovenerology. 相似文献