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Structurally based, selective interaction of arsenite with steroid receptors
S Lopez1, Y Miyashita, S S Simons
1Steroid Hormones Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892.
The Journal of Biological Chemistry
|September 25, 1990
Summary
Arsenite selectively inhibits steroid binding to glucocorticoid receptors by targeting a unique vicinal dithiol group. This discovery offers a precise method for differentiating between glucocorticoid and mineralocorticoid receptors.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Steroid receptors bind ligands with high affinity, but specificity is limited by homologous binding domains.
- A vicinal dithiol group within the 16-kDa core is implicated in glucocorticoid receptor steroid binding.
Purpose of the Study:
- To investigate the selectivity of arsenite as an inhibitor of steroid binding to various steroid receptors.
- To leverage structural differences in cysteine placement for selective receptor interaction.
Main Methods:
- Comparative analysis of cysteine placement in steroid receptor binding domains.
- Testing the effect of 100 microM arsenite on steroid binding to glucocorticoid, androgen, estrogen, mineralocorticoid, and progesterone receptors.
Main Results:
- Arsenite completely inhibited steroid binding to glucocorticoid receptors.
- Arsenite showed no effect on steroid binding to androgen, estrogen, mineralocorticoid, or progesterone receptors.
- Selenite, another inhibitor, did not exhibit this absolute selectivity.
Conclusions:
- Arsenite demonstrates absolute selectivity for inhibiting steroid binding to glucocorticoid receptors, based on a unique vicinal dithiol structural feature.
- This selectivity provides a straightforward method for distinguishing glucocorticoid from mineralocorticoid receptors and for selectively blocking glucocorticoid receptor binding.