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Updated: Aug 15, 2026
10:21
Protein Target Prediction and Validation of Small Molecule Compound
Published on: February 23, 2024
Molecular conformation and protein binding affinity of progestins
Journal of Toxicology and Environmental Health
|March 1, 1978
Summary
Steroid hormones exhibit flexibility, adopting optimal conformations for protein binding. An inverted A ring is proposed as the key factor for progestin receptor binding affinity.
Area of Science:
- Steroid chemistry
- Structural biology
- Molecular endocrinology
Background:
- Natural steroid hormones possess inherent flexibility, allowing adaptation to diverse protein binding sites.
- Structural analysis reveals how substituents influence steroid conformation and receptor interactions.
Purpose of the Study:
- To analyze X-ray data of 277 steroid molecules (estranes, androstanes, pregnanes).
- To compare structural data with progesterone receptor binding affinities.
- To elucidate conformational factors governing steroid-receptor interactions.
Main Methods:
- X-ray crystallography of steroid compounds.
- Comparative analysis of molecular structures and binding data.
- Conformational analysis of steroid skeletons.
Main Results:
- Steroid flexibility enables optimal binding conformations.
- Substituents can stabilize specific conformations, influencing hormone response.
- The delta4-3-one moiety is crucial for progestin receptor binding.
- An inverted A ring conformation is identified as optimal for high-affinity binding.
Conclusions:
- The inverted A ring conformation is proposed as a primary determinant of progestin receptor binding.
- Hydrogen bond patterns in crystals can predict receptor attachment sites.
- The D-ring region offers flexibility for receptor or genome interactions.
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