NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses.

ABSTRACT: Our understanding of how steroid hormones regulate physiological functions has been significantly advanced by structural biology approaches. However, progress has been hampered by misfolding of the ligand binding domains in heterologous expression systems and by conformational flexibility that interferes with crystallization. Here, we show that protein folding problems that are common to steroid hormone receptors are circumvented by mutations that stabilize well-characterized conformations of the receptor. We use this approach to present the structure of an apo steroid receptor that reveals a ligand-accessible channel allowing soaking of preformed crystals. Furthermore, crystallization of different pharmacological classes of compounds allowed us to define the structural basis of NFkappaB-s

SUBMITTER: Nettles KW 

PROVIDER: S-EPMC2659626 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature