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Ligand Induced Solution Structure and Dynamics of the Helix‐12 region of Estrogen Receptor Alpha
Author(s) -
Gulla Stefano Vincenzo,
Budil David E
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a253-b
Subject(s) - chemistry , ligand (biochemistry) , helix (gastropod) , mutant , estrogen receptor alpha , biophysics , electron paramagnetic resonance , nitroxide mediated radical polymerization , molecular dynamics , agonist , estrogen receptor , binding site , crystallography , stereochemistry , receptor , nuclear magnetic resonance , computational chemistry , physics , biochemistry , biology , genetics , ecology , radical polymerization , organic chemistry , cancer , snail , gene , breast cancer , copolymer , polymer
The objective of the study is to elucidate the solution structure of the functionally important helix‐12 region in the ligand binding domain of human estrogen receptor alpha (hER‐á‐LBD). We used site directed spin labeling to introduce a nitroxide probe at the 530 and 543 positions of hER‐á‐LBD. EPR lineshape fitting of rotational diffusion parameters was used to measure chain mobility in response to binding of agonist/partial‐antagonist/antagonist ligands for the singly labeled mutants. Ligand dependent inter‐spin distances for the doubly labeled mutant (530–543) were measured using the dipolar broadening method. The data provides the necessary information to describe the dynamic as well as structural response of the H12 region of ER to ligand binding. The work shows the integration of dynamic diffusion parameters with distance measurements to ascertain the effect of ligands on the solution structure of hER‐á‐LBD.