PMID: 11909639Mar 23, 2002Paper

Modification of an essential amino group in the mineralocorticoid receptor evidences a differential conformational change of the receptor protein upon binding of antagonists, natural agonists and the synthetic agonist 11,19-oxidoprogesterone

Biochimica Et Biophysica Acta
G Piwien-PilipukMario D Galigniana

Abstract

The alkylation of amino groups of the mineralocorticoid receptor (MR) with pyridoxal 5'-phosphate or 2,4,6-trinitrobenzenesulphonate (TNBS) under controlled conditions modifies only one lysyl residue, which accounts for a 70% inhibition of steroid binding capacity. The Kd of aldosterone for MR is not affected by the treatment, but the total number of binding sites is greatly decreased. The modified receptor is capable of dynamically conserving its association with the hsp90-based heterocomplex. Importantly, the binding of natural agonists protects the hormone binding capacity of the MR from the inactivating action of alkylating agents. In contrast, antagonistic steroids are totally incapable of providing such protection. Like the antagonistic ligands, and despite its potent mineralocorticoid biological effect, the sole MR specific synthetic agonist known to date, 11,19-oxidoprogesterone (11-OP), shows no protective effect upon treatment of the MR with pyridoxal 5'-phosphate or TNBS. Limited digestion of the MR with alpha-chymotrypsin generates a 34 kDa fragment, which becomes totally resistant to digestion upon binding of natural agonists, but not upon binding of antagonists. Interestingly, the synthetic 21-deoxypregnanesteroid...Continue Reading

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Oct 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·Z S Krozowski, J W Funder
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Citations

Nov 8, 2002·European Journal of Pharmacology·Graciela Piwien-PilipukMario D Galigniana
Mar 7, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Gisela I MazairaMario D Galigniana
Jul 7, 2021·Journal of Chemical Information and Modeling·Kei TakedomiMitsunori Ikeguchi

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