共查询到20条相似文献,搜索用时 31 毫秒
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P M Elias 《The Western journal of medicine》1988,149(6):766-767
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Tom Keenan 《CMAJ》1988,138(7):654-655
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Unbinding of retinoic acid from the retinoic acid receptor by random expulsion molecular dynamics
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Unbinding pathways of retinoic acid (RA) bound to retinoic acid receptor (RAR) have been explored by the random expulsion molecular dynamics (REMD) method. Our results show that RA may exit the binding site of RAR through flexible regions close to the H1-H3 loop and beta-sheets, without displacing H12 from its agonist position. This result may explain kinetic differences between agonist and antagonist ligands observed for other nuclear receptors. The extended and flexible structure of RA initiated a methodological study in a simplified two-dimensional model system. The REMD force should in general be distributed to all atoms of the ligand to obtain the most unbiased results, but for a ligand which is tightly bound in the binding pocket through a strong electrostatic interaction, application of the REMD force on a single atom is preferred. 相似文献
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Julius Brtko Peter Filipčík Soňa Hudecová Anastázia Brtková Janette Bransová 《Biological trace element research》1998,62(1-2):43-50
The present study was undertaken to investigate the effects of selenite (SeIV) and selenate (SeVI) on the all-trans retinoic acid (RA)-nuclear retinoic acid receptor (RAR) complex formation in rat liver. We also present
the data on the in vitro effects of SeIV on the RARα and the type I iodothyronine 5′-deiodinase gene expression in the GH4C1 rat pituitary tumor cells. SeIV at 1.0 μmol/L was found to reduce (p<0.05) the RA specific binding to RAR in rat liver. Dithiothreitol (DTT), a protective agent for sulfhydryl groups, was found
to be slightly effective in protecting the RAR binding properties when affected by SeIV. SeVI at 0.1 μmol/L reduced (p<0.05) the RA specific binding to RAR in liver, as well. Seleno-l-methionine (Se-II) when compared tol-methionine did not exert any inhibitory effect on the formation of the RA-RAR complex. SeIV (up to 2.5 μmol/L) has no inhibitory effect on GH4C1 cell proliferation as well as the prolactin secretion. SeIV at 1.0 μmol/L significantly decreases the rate of mRNA synthesis and/or degradation of the α form of the RAR and causes the
enhancement of the type I iodothyronine 5′-deiodinase gene expression in GH4C1 cells.
The results based on in vitro experiments suggest that inorganic selenium may affect the RA specific binding to their cognate
receptor molecules, and it may reduce expression of the gene encoding the RARα, with the cell vitality and the cell growth
remaining unchanged. 相似文献
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Tirumala Harikrishna Anantha Krishna Subban Kamalraj Maheswaraiah Anikisetty K. Akhilender Naidu William R. Surin Chelliah Jayabaskaran 《Biochemistry and Biophysics Reports》2019
Retinoic acid, a derivative of vitamin A, is known to possess in vivo anti-inflammatory, anti-platelet and fibrinolytic activities. We have investigated the in vitro thrombin and platelet aggregation inhibitory activities of vitamin A (retinol) and its derivatives, retinoic acid and retinaldehyde. The thrombin enzymatic assay was performed fluorimetrically to assess the inhibition of thrombin (Sigma and plasma). Retinoic acid, retinaldehyde and retinol exhibited potent inhibition of thrombin, with IC50 values of 67μg/ml, 74μg/ml and 152μg/ml, respectively for the inhibition of thrombin (Sigma); and 49μg/ml, 74μg/ml and 178μg/ml, respectively for the inhibition of thrombin (plasma). Amongst vitamin A and its derivatives, retinoic acid showed the highest inhibition of both the forms of thrombin. Vitamin A and its derivatives also displayed remarkable inhibition of platelet aggregation. This is the first report of vitamin A and its derivatives showing inhibition of thrombin and platelet aggregation in vitro. 相似文献
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Allegrone G Brenna E Fronza G Fuganti C Giovenzana T Malpezzi L Barlocchi E Pellegatta C 《Bioorganic & medicinal chemistry letters》2005,15(15):3528-3531
The structure of an impurity contained in samples of all trans-retinoic acid was established by means of NMR and MS spectra, and confirmed by X-ray diffraction analysis. The chemical structure of the impurity 2 was found to be strictly correlated to the synthetic procedure employed for the preparation of the retinoic acid samples. Single crystal analysis allowed us to characterise the molecular conformation and the crystal structure of 2. 相似文献
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Mark Donovan Birgitta Olofsson Anne-Lee Gustafson Lennart Dencker Ulf Eriksson 《The Journal of steroid biochemistry and molecular biology》1995,53(1-6):459-465
The two cellular retinoic acid binding proteins, CRABP I and CRABP II, belong to a family of small cytosolic lipid binding proteins and are highly conserved during evolution. Both proteins are expressed during embryogenesis, particularly in the developing nervous system, craniofacial region and limb bud. CRABP I is also expressed in several adult tissues, however, in contrast, CRABP II expression appears to be limited to the skin. It is likely that these proteins serve as regulators in the transport and metabolism of retinoic acid in the developing embryo and throughout adult life. It has been proposed that CRABP I sequesters retinoic acid in the cytoplasm and prevents nuclear uptake of retinoic acid. A role in catabolism of retinoic acid has also been proposed. Recent gene targeting experiments have shown that neither of the two CRABPs are essential for normal embryonic development or adult life. Examination of CRABP I expression at subcellular resolution reveals a differential cytoplasmic and/or nuclear localization of the protein. A regulated nuclear uptake of CRABP I implies a role for this protein in the intracellular transport of retinoic acid. A protein mediated mechanism which controls the nuclear uptake of retinoic acid may play an important role in the transactivation of the nuclear retinoic acid receptors. 相似文献
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M Husmann J Lehmann B Hoffmann T Hermann M Tzukerman M Pfahl 《Molecular and cellular biology》1991,11(8):4097-4103
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Rat testes cytosol treated by Blue Sepharose was employed in a simple and sensitive method for the determination of retinoic acid in the rat serum, liver, and intestine. The method permits the detection of as little as 3 ng of retinoic acid. The mean concentrations of retinoic acid in normal male rats were 33.5 ng/ml of serum, 624.9 ng/g wet wt of liver, and 444.3 ng/g of intestine. 相似文献
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Gene expression regulation by retinoic acid 总被引:16,自引:0,他引:16
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Goyette P Feng Chen C Wang W Seguin F Lohnes D 《The Journal of biological chemistry》2000,275(22):16497-16505
Retinoids are essential for normal epidermal growth and differentiation and show potential for the prevention or treatment of various epithelial neoplasms. The retinoic acid receptors (RARalpha, -beta, and -gamma) are transducers of the retinoid signal. The epidermis expresses RARgamma and RARalpha, both of which are potential mediators of the effects of retinoids in the epidermis. To further investigate the role(s) of these receptors, we derived transformed keratinocyte lines from wild-type, RARalpha, RARgamma, and RARalphagamma null mice and investigated their response to retinoids, including growth inhibition, markers of growth and differentiation, and AP-1 activity. Our results indicate that RARgamma is the principle receptor contributing to all-trans-retinoic acid (RA)-mediated growth arrest in this system. This effect partially correlated with inhibition of AP-1 activity. In the absence of RARs, the synthetic retinoid N-(4-hydroxyphenyl)-retinamide inhibited growth; this was not observed with RA, 9-cis RA, or the synthetic retinoid (E)-4-[2-(5, 5, 8, 8 tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propenyl] benzoic acid. Finally, both RARalpha and RARgamma differently affected the expression of some genes, suggesting both specific and overlapping roles for the RARs in keratinocytes. 相似文献