Bledsoe Randy K, Stewart Eugene L, Pearce Kenneth H
Department of Gene Expression and Protein Biochemistry, Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA.
Vitam Horm. 2004;68:49-91. doi: 10.1016/S0083-6729(04)68002-2.
After binding to an activating ligand, such as corticosteroid, the glucocorticoid receptor (GR) performs an impressive array of functions ranging from nuclear translocation, oligomerization, cofactor/kinase/transcription factor association, and DNA binding. One of the central functions of the receptor is to regulate gene expression, an activity triggered by ligand binding. In this role, GR acts as an adapter molecule by encoding the ligand's message within the structural flexibility of the ligand binding domain (LBD). The purpose of this review is to discuss the many structural and functional features of the GR LBD in light of recent successful biochemical and crystallographic studies. Progress in this area of research promises to reveal new strategies and insights allowing for the design of novel drugs to treat inflammatory diseases, diabetic conditions, steroid resistance, and cancers.
与诸如皮质类固醇等激活配体结合后，糖皮质激素受体（GR）会执行一系列令人瞩目的功能，包括核转位、寡聚化、辅因子/激酶/转录因子结合以及DNA结合。该受体的核心功能之一是调节基因表达，这一活性由配体结合触发。在这一作用中，GR通过在配体结合域（LBD）的结构灵活性内编码配体信息，充当衔接分子。本综述的目的是根据近期成功的生化和晶体学研究，讨论GR LBD的诸多结构和功能特征。该研究领域的进展有望揭示新的策略和见解，从而设计出治疗炎症性疾病、糖尿病、类固醇抵抗和癌症的新型药物。
