Work

G Protein‐Coupled Estrogen Receptor (GPER) Agonist Dual Binding Mode Analyses Toward Understanding of Its Activation Mechanism: A Comparative Homology Modeling Approach

Year: 2013

Type: article

Abstract: G protein‐coupled estrogen receptor (GPER) has been shown to be important in several disease states such as estrogen sensitive cancers. While several selective ligands have been identified for the receptor, little is known about how they interact with GPER and how their structures influence their activity. Specifically, within one series of ligands, whose structure varied only at one position, the replacement of a hydrogen atom with an acetyl group changed a potent antagonist into a potent agonist. In this study, two GPER homology models were constructed based on the X‐ray crystal structures of both the active and inactive β2‐adrenergic receptors (β2AR) in an effort to characterize the differences of binding modes between agonists and antagonists to the receptor, and to understand their activity in relation to their structures. The knowledge attained in this study is expected to provide valuable information on GPER ligands structure activity relationship to benefit future rational design of potent agonists and antagonists of the receptor for potential therapeutic applications.

Source: Molecular Informatics

DOI: 10.1002/minf.201200136

Authors: Christopher K. Arnatt, Yan Zhang

Institution: Virginia Commonwealth University

Language: English

Topic: Receptor Mechanisms and Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute on Drug Abuse