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Matches in SemOpenAlex for { <https://semopenalex.org/work/W1998804942> ?p ?o ?g. }

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• W1998804942 abstract "The human estrogen receptor (hER) is a ligand-activated transcription factor which, like many other members of the nuclear receptor protein family, exhibits a dimerization-dependent transcriptional activation. Several previous reports have provided evidence of the phosphorylation of the hER at tyrosine 537 (Y537). However, the exact function of a putative phosphorylation at this site remains controversial. Using a yeast transactivation assay, and in vitro biochemical approaches, we show that phosphorylation of tyrosine 537 is not required for the hER to bind hormone, or to activate transcription. An hER tyrosine 537 to phenylalanine (Y537F) mutant retains 70−75% of the transactivation potential of wild type hER in a yeast reporter system. Furthermore, the mutated receptor exhibits wild type hormone and DNA binding affinities. However, this mutation results in a decrease in receptor stability as measured by a decrease in the extent of hormone binding over time. The most striking difference between the wild type and Y537F hER is in the estradiol binding kinetics. Whereas the off-rate for estradiol exhibits a two-state binding mechanism, the Y537F mutant hER exhibits a monophasic estradiol off-rate. On the basis of these data and other reports describing the structure and activity of Y537 mutations, as well as knowledge of the three-dimensional structure of the hER ligand binding domain, we propose an alternate model wherein Y537F mutation favors an “open” pocket conformation, affecting the estrogen binding kinetics and stability of the hormone-bound, transcriptionally active “closed” pocket conformation. Although its phosphorylation is not essential for function of the hER, Y537 is nevertheless a critical residue intricately involved with the conformational changes of the hER and its ability to activate transcription." @default.
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• W1998804942 date "1999-10-01" @default.
• W1998804942 modified "2023-10-09" @default.
• W1998804942 title "Function of Estrogen Receptor Tyrosine 537 in Hormone Binding, DNA Binding, and Transactivation" @default.
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• W1998804942 doi "https://doi.org/10.1021/bi9911132" @default.
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