Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The untransformed rat glucocorticoid receptor is assumed to be a hetero-oligomeric complex, containing a non-steroid binding component, the 90K heat-shock protein (HSP 90). Direct measurement of its molecular weight by chemical cross-linking provides new evidence for a trimeric structure with a Mr of ca. 270,000. Resorting to an anti HSP 90 probe (AC 88), we show that the native dimeric HSP 90 possess two accessible epitopes for this monoclonal antibody, while when bound to the steroid-binding subunit, only one epitope remains accessible. These data clearly suggest that the untransformed rat glucocorticoid receptor is an asymmetrical hetero-oligomeric complex.
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PMID:Study of the heteromeric structure of the untransformed glucocorticoid receptor using chemical cross-linking and monoclonal antibodies against the 90K heat-shock protein. 293 May 36

The molecular properties of the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse hepatoma cell line Hepa 1c1c7 were investigated. The receptor was found to represent a highly asymmetrical molecule with a sedimentation coefficient, s20,w, of approximately 8 S, a Stokes radius of 7-8 nm, and a calculated Mr approximately equal to 260,000-300,000. In comparison, the Hepa 1c1c7 glucocorticoid receptor in analogy to the glucocorticoid receptor in general as well as the C57BL/6 mouse and rat hepatic dioxin receptors are molecules with an s20,w value of 4-5 S, a Stokes radius of approximately 6 nm, and a calculated Mr approximately equal to 100,000. In the presence of 20 mM sodium molybdate, a large Mr approximately equal to 270,000-310,000 form of the Hepa 1c1c7 glucocorticoid receptor is stabilized which is hydrodynamically indistinguishable from the Mr approximately equal to 260,000-300,000 Hepa 1c1c7 dioxin receptor. Sodium molybdate does not have any effect on the molecular properties of the Hepa 1c1c7 dioxin receptor. In conclusion, the large form of dioxin receptor present in Hepa 1c1c7 mouse hepatoma cells in the absence of sodium molybdate is strikingly similar to molybdate-stabilized steroid hormone receptors as well as the molybdate-stabilized form of the dioxin receptor previously demonstrated in rat hepatic cytosol. Therefore, the Hepa 1c1c7 dioxin receptor might offer an interesting model for studies on the structure and function of Mr approximately equal to 300,000 forms of soluble receptors.
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PMID:The receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse hepatoma cell line Hepa 1c1c7. A comparison with the glucocorticoid receptor and the mouse and rat hepatic dioxin receptors. 302 14

The physico-chemical properties of the dioxin and glucocorticoid receptors from rat liver and wild-type and mutant cell lines were investigated and compared. In rat liver, the receptors are virtually indistinguishable. Both are highly asymmetrical proteins with axial ratios of 12-15, have Stokes radii of 6 nm and sedimentation coefficients of approximately 4 S. This results in a calculated apparent mol. wt of approximately 100,000. The dioxin receptor from the mouse hepatoma cell line Hepa 1c1c7 represents an atypical form of the dioxin receptor with a pronounced tendency to aggregate to form Mr approximately equal to 300,000 complexes in high ionic strength and in the absence of sodium molybdate. In the presence of sulphydryl reducing agents, however, the Hepa 1c1c7 dioxin receptor dissociates to an Mr approximately 100,000 species. In analogy to the nt- mutant glucocorticoid receptor in mouse lymphoma cells, there is no gross change in the structure of the nt- dioxin mutant in mouse hepatoma cells compared with the wild-type receptor. The nt- dioxin receptor does, however, have a reduced affinity for DNA.
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PMID:The dioxin receptor: a comparison with the glucocorticoid receptor. 338 53

A major impediment of many QSAR-type analyses is that the data show a maximum or minimum and can no longer be adequately described by linear functions that provide unrivaled simplicity and usually give good description over more restricted ranges. Here, a general linearized biexponential (LinBiExp) model is proposed that can adequately describe data showing bilinear-type distribution as a function of not just often-employed lipophilicity descriptors (e.g., log P) but as a function of any descriptor (e.g., molecular volume). Contrary to Hansch-type parabolic models, LinBiExp allows the natural extension of linear models and fitting of asymmetrical data. It is also more general and intuitive than Kubinyi's model as it has a more natural functional form. It was obtained by a differential equation-based approach starting from very general assumptions that cover both static equilibria and first-order kinetic processes and that involve abstract processes through which the concentration of the compound of interest in an assumed "effect" compartment is connected to its "external" concentration. Physicochemical aspects placing LinBiExp within the framework of linear free energy relationship (LFER) approaches are presented together with illustrative applications in various fields such as toxicity, antimicrobial activity, anticholinergic activity, and glucocorticoid receptor binding.
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PMID:General linearized biexponential model for QSAR data showing bilinear-type distribution. 1620 May 70

Infant neurobehavior, a potential sentinel of future mental and behavioral morbidity characterized in part by reflex symmetry, excitability and habituation to stimuli, is influenced by aspects of the intrauterine environment partially through epigenetic alterations of genes involved in the stress response. DNA methylation of two related cortisol response genes, the glucocorticoid receptor (NR3C1), a nuclear receptor to which cortisol binds, and 11-beta hydroxysteroid dehydrogenase (HSD11B2), the enzyme responsible for conversion of cortisol into inactive cortisone, independently associate with infant neurobehavior. Although these factors are part of a common cortisol regulation pathway, the combined effect of DNA methylation of these factors on infant neurobehavior has not been characterized. Therefore, we conducted an examination of the joint contribution of NR3C1 and HSD11B2 DNA methylation on infant neurobehavior. Among 372 healthy term newborns, we tested the interaction between placental NR3C1 and HSD11B2 DNA methylation in association with neurobehavior as assessed with the validated NICU Network Neurobehavioral Scales. Controlling for confounders, interactions between DNA methylation of these genes were detected for distinct domains of neurobehavior (habituation, excitability, asymmetrical reflexes). Moreover, different patterns of DNA methylation across the cortisol regulation pathway associated with different neurobehavioral phenotypes. Those with low NR3C1 methylation but high HSD11B2 methylation had lower excitability scores; those with high NR3C1 methylation but low HSD11B2 methylation had more asymmetrical reflexes; those with high DNA methylation across the entire pathway had higher habituation scores. These results suggest that epigenetic alterations across the cortisol regulation pathway may contribute to different neurobehavioral phenotypes, likely though varying degrees of glucocorticoid exposure during gestation. While the postnatal environment may continue to affect neurobehavioral risk, this study provides novel insights into the molecular basis for fetal origins of mental conditions.
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PMID:Examining the joint contribution of placental NR3C1 and HSD11B2 methylation for infant neurobehavior. 2545 91