AI Article Synopsis
- RU486 is an effective anti-progestin in humans but fails to work in chickens and hamsters due to a specific change in the progesterone receptor structure (cysteine instead of glycine at position 722).
- The tammar wallaby also shows resistance to RU486, having unique amino acid substitutions in its progesterone receptor that differ from humans.
- These changes in amino acids are linked to the binding properties of the receptor and suggest significant roles for certain residues in accommodating steroid hormones, indicating broader implications for receptor function across different species.
Article Abstract
RU486 acts as a potent anti-progestin in humans but does not antagonise progesterone action in the chicken or hamster reflecting a substitution in the ligand binding domain (LBD) of cysteine for glycine in both the chicken and the hamster progesterone receptor (PR), at the position corresponding to codon 722 of the human PR. The tammar wallaby, Macropus eugenii, is also resistant to the effects of RU486. Cloning of a partial cDNA of the PR in the tammar wallaby reveals a glycine to alanine substitution (gly 722 in the human PR), as well as a glutamine to histidine substitution two amino acids upstream of this alanine residue. Both the glycine and glutamine residues are substituted in all three resistant species. These substitutions are also found in the mineralocorticoid receptor, which also does not bind RU486, and suggest an important role for these residues in the formation of the 11-beta pocket of the receptor, which accommodates the bulky side-chains of 11-beta substituted steroids.
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| http://dx.doi.org/10.1016/0303-7207(96)03807-5 | DOI Listing |
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