title: Comparison of 17beta-estradiol structures from x-ray diffraction and solution NMR.
abstract: The NMR-derived structure of estrogen (17beta-estradiol, E2), the drug of choice for postmenopausal women, was compared with a recent literature crystal x-ray structure of Fab-bound E2. 1H and 13C NMR spectra of E2 were acquired in DMSO-d6. Assignments were obtained from an analysis of DQF-COSY, TOCSY, HETCOR, HMQC and HMBC 2D NMR spectra. The 1H and 13C NMR assignments are the first reported for E2 in DMSO-d6. Two solution structures, S1 and S2, were obtained with molecular modeling using NOE constraints. S1 overlaps with the crystal structure for all rings. S2 shows prominent differences in the C-ring (C9--C11--C12--C13) segment, which deviates from a chair conformation, and excellent overlap in the A-, B- and D-rings of E2. The C-ring in S2 adopts a boat conformation as opposed to a chair conformation in the x-ray and S1 structures. The S2 structure is about 6 degrees more twisted than the bound x-ray and S1 models. The S1, S2 and x-ray structures had ring bowing values of 10.1 +/- 0.3, 11 +/- 1 and 10.37 degrees , respectively. Of the 100 solution conformers generated, 83 had S1 conformation and 17 had S2 conformation, with average internal energies of 112 +/- 2 and 141 +/- 2 kcal mol(-1), respectively. The 100 S1- and S2- derived conformers showed a r.m.s.d. of 0.72 A for all atoms. The x-ray, S1 and S2 C18--O17 distances were 2.93, 2.92 +/- 0.01 and 2.93 +/- 0.01 A, respectively, and the O3--O17 distances were 11.06, 11.18 +/- 0.12, and 10.89 +/- 0.05 A, respectively.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 10461, USA. fern@medusa.bioc.aecom.yu.edu
authors.forename: Fernando
authors.initials: F
authors.lastname: Commodari
authors.forename: George
authors.initials: G
authors.lastname: Sclavos
authors.forename: Sanae
authors.initials: S
authors.lastname: Ibrahimi
authors.forename: Abdesslem
authors.initials: A
authors.lastname: Khiat
authors.forename: Yvan
authors.initials: Y
authors.lastname: Boulanger
mesh_terms: D002247:Carbon Isotopes; D004958:Estradiol / Q000737:chemistry*; D021621:Imaging, Three-Dimensional; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D015394:Molecular Structure; D011522:Protons; D014961:X-Ray Diffraction
chemical_list: D002247:Carbon Isotopes; D011522:Protons; D004958:Estradiol