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Unique Ligand Binding Patterns between Estrogen Receptor α and β Revealed by HydrogenβDeuterium Exchange.

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Title: Unique Ligand Binding Patterns between Estrogen Receptor α and β Revealed by HydrogenβDeuterium Exchange.
Authors: Dai, Susie Y.1,2, Burris, Thomas P.3,4, Dodge, Jeffrey A.3, Montrose-Rafizadeh, Chahrzad3, Yong Wang3, Pascal, Bruce D.5, Chalmers, Michael J.1,5, Griffin, Patrick R.1,5 pgriffin@scripps.edu
Source: Biochemistry. 10/13/2009, Vol. 48 Issue 40, p9668-9676. 9p.
Subjects: Mass spectrometry, Ligand binding (Biochemistry), Quantum perturbations, Chemical structure, Physical & theoretical chemistry
Abstract: Here we present the use of hydrogen—deuterium exchange (HDX) mass spectrometry in analyzing the estrogen receptor/S ligand binding domain (ERβ LBD) in the absence and presence of a variety of chemical compounds with different binding modes and pharmacological properties. Previously, we reported the use of HDX nsa method for predicting the tissue selectivity of ERrs ligands. HDX profiles of ERα LBD in complex with ligand could differentiate compounds of the same chemotype. In contrast, similar analysis of ERβ LBD showed correlation to the compound chemical structures but little correlation with compound tissue selectivity. The different HDX patterns observed for ERβ LBD when compared to those for ERβ LBD bound to the same chemical compounds serve as an indication that ERβ LBD undergoes a different structural response to the same ligand when compared to ERα LBD. The conformational dynamics revealed by HDX for ERβ LBD together with those for ERα LBD shed light on ER ligand interactions and offer new structural insights. The compound-specific perturbations in HDX kinetics observed for each of the two isoforms should aid the development of subtype-selective ER ligands. [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
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Abstract:Here we present the use of hydrogen—deuterium exchange (HDX) mass spectrometry in analyzing the estrogen receptor/S ligand binding domain (ERβ LBD) in the absence and presence of a variety of chemical compounds with different binding modes and pharmacological properties. Previously, we reported the use of HDX nsa method for predicting the tissue selectivity of ERrs ligands. HDX profiles of ERα LBD in complex with ligand could differentiate compounds of the same chemotype. In contrast, similar analysis of ERβ LBD showed correlation to the compound chemical structures but little correlation with compound tissue selectivity. The different HDX patterns observed for ERβ LBD when compared to those for ERβ LBD bound to the same chemical compounds serve as an indication that ERβ LBD undergoes a different structural response to the same ligand when compared to ERα LBD. The conformational dynamics revealed by HDX for ERβ LBD together with those for ERα LBD shed light on ER ligand interactions and offer new structural insights. The compound-specific perturbations in HDX kinetics observed for each of the two isoforms should aid the development of subtype-selective ER ligands. [ABSTRACT FROM AUTHOR]
ISSN:00062960
DOI:10.1021/bi901149t