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J. Biol. Chem., Vol. 266, Issue 33, 22075-22078, 11, 1991
PK Chakraborti, MJ Garabedian, KR Yamamoto and SS Simons Jr
Almost all modifications of the steroid binding domain of glucocorticoid
receptors are known to cause a reduction or loss of steroid binding
activity. Nonetheless, we now report that mutations of cysteine 656 of the
rat receptor, which was previously suspected to be a crucial amino acid for
the binding process, have produced "super" receptors. These receptors
displayed an increased affinity for glucocorticoid steroids and a decreased
relative affinity for cross- reacting steroids such as progesterone and
aldosterone. The increased in vitro affinity of the super receptors was
maintained in a whole cell bioassay. These results indicate that additional
modifications of the glucocorticoid receptor, and probably the other
steroid receptors, may further increase the binding affinity and/or
specificity.
Creation of "super" glucocorticoid receptors by point mutations in the steroid binding domain
Steroid Hormones Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
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