Accession Number:

ADB238997

Title:

Substrate Induced Conformational Studies of the Hormone Binding Domain of the Human Estrogen Receptor by Fluorine NMR

Descriptive Note:

ANNUAL REPT. 1 JUL 97-30 JUN 98

Corporate Author:

CLARKSON UNIV POTSDAM NY

Personal Author(s):

Report Date:

1998-07-01

Pagination or Media Count:

43.0

Abstract:

Estrogen has been shown to be involved in the progression of breast cancer and the estrogen receptor ER has been implicated in reproductive cancers. Our laboratory would like to understand how the structure of the hormone binding domain HBD of the ER changes when it is activated by estrogens and anti-estrogens. Since the binding of estradiol to its receptor ultimately leads to diverse biological responses to the hormone, we would like to investigate the response of the receptor to a series of ligands and illucidate the molecular basis for their functional differences. This proposal will characterize the critical substrate induced conformational changes in the HBD by incorporating fluorine labels into two recombinate constructs and performing fluorine nuclear magnetic resonance NMR studies. We will examine whether estrogens and antiestrogens produce similar conformational effects on the receptor and will compare these changes to those induced by environmental estrogens. The purpose of this proposal is to provide and understand the conformational changes in HBD which will shed light on the molecular events of substrate binding, transcriptional activation and the role of environmental estrogens in receptor function.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research
  • Radiobiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE