Journal article
Molecular details of receptor binding and hormonal action of steroids derived from X-ray crystallographic investigations
Journal of steroid biochemistry, Vol.15(C), pp.41-47
12/1981
DOI: 10.1016/0022-4731(81)90256-9
PMID: 7339269
Abstract
Analysis of X-ray crystallographic data on steroids provides information concerning preferred conformations, relative stabilities, and substituent influence on the interactive potential of steroid hormones. Analysis of the data on the 4-ene-3-one ring indicates that it normally has a conformation midway between the 1α,2β-half chair and the 1α-sofa forms. Strain introduced into the molecule by substitution on the fused ring system shifts the A-ring conformation toward the more symmetric forms with an attendant change in the conjugation of the 4-ene-3-one system. Crystallographic data on 85 pregnane structures having a 20-one substituent provide information on 17β-side chain flexibility. In eighty-one structures the C(16)-C(17)-C(20)-O(20) torsion angle is between 0° and −46°. This is consistent with CD, i.r. and n.m.r. solution spectra and more precisely defines the side chain conformation in solution. The four structures whose side chains lie outside this range do so because of the presence of a 16β-substituent and not because of crystal packing forces. The steroid A ring appears to be primarily responsible for initiating and maintaining hormone binding to the estrogen and progestin receptors. When the structures of agonists and antagonists of specific steroid hormones are compared, they generally exhibit similarities in their A-ring region and dissimilarities in the D-ring region further suggesting that the steroid A-ring bears responsibility for receptor binding while the D-ring controls expression of activity. Antihormoncs that compete for the receptor site of a steroid hormone may be expected to have structural features appropriate for receptor binding (A-ring composition and conformation) and lack structural features that induce or stabilize subsequent receptor functions (D-ring conformatjonal features and functional groups).
Details
- Title: Subtitle
- Molecular details of receptor binding and hormonal action of steroids derived from X-ray crystallographic investigations
- Creators
- W.L. Duax - The Medical FoundationJ.F. Griffin - The Medical FoundationD.C. Rohrer - The Medical FoundationD.C. Swenson - The Medical FoundationC.M. Weeks - The Medical Foundation
- Resource Type
- Journal article
- Publication Details
- Journal of steroid biochemistry, Vol.15(C), pp.41-47
- Publisher
- Elsevier B.V
- DOI
- 10.1016/0022-4731(81)90256-9
- PMID
- 7339269
- ISSN
- 0022-4731
- eISSN
- 1879-1220
- Language
- English
- Date published
- 12/1981
- Academic Unit
- Chemistry
- Record Identifier
- 9984622749502771
Metrics
4 Record Views