Differences in the binding mechanism of RU486 and progesterone to the progesterone receptor

Journal Article · Tue Nov 12 00:00:00 EST 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00109a003· OSTI ID:5687348

Skafar, D F ^[1]

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1. Wayne State Univ., Detroit, MI (United States)

The binding mechanism of the antagonist RU486 to the progesterone receptor was compared with that of the agonists progesterone and R5020. Both progesterone and RU486 bound to the receptor with a Hill coefficient of 1.2, indicating the binding of each ligand is positive cooperative. However, when each ligand was used to compete with ({sup 3}H)progesterone for binding to the receptor at receptor concentrations near 8 nM, at which the receptor is likely a dimer, the competition curve for RU486 was significantly steeper than the curves for progesterone and R5020. This indicated that a difference in the binding mechanism of RU486 and progesterone can be detected when both ligands are present. In contrast, at receptor concentrations near 1 nM, at which the receptor is likely a monomer, the competition curves for all three ligands were indistinguishable. These results indicate that RU486 and agonists have different binding mechanisms for the receptor and further suggest that this difference may be related to site-site interactions within the receptor.

• OSTI ID: 5687348
• Journal Information: Biochemistry; (United States), Vol. 30:45; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
PROGESTERONE
RADIORECEPTOR ASSAY
RECEPTORS
CONFORMATIONAL CHANGES
BIOCHEMICAL REACTION KINETICS
CALVES
TRITIUM COMPOUNDS
UTERUS
ANIMALS
BODY
CATTLE
DOMESTIC ANIMALS
FEMALE GENITALS
HORMONES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KETONES
KINETICS
MAMMALS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
ORGANS
PREGNANES
PROTEINS
REACTION KINETICS
RUMINANTS
STEROID HORMONES
STEROIDS
TRACER TECHNIQUES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques