Zhang Junhui, Geller David S
Section of Nephrology, Yale University School of Medicine, New Haven, CT 06520-8029, USA.
J Steroid Biochem Mol Biol. 2008 Apr;109(3-5):279-85. doi: 10.1016/j.jsbmb.2008.03.018. Epub 2008 Mar 13.
Steroid hormones working through their receptors regulate a wide variety of physiologic processes necessary for normal homeostasis. Recent years have witnessed great advances in our understanding of how these hormones interact with their receptors, and have brought us closer to the era of directed drug design. We previously described a novel intramolecular interaction between helix 3 and helix 5 which is responsible for a Mendelian form of human hypertension. Further studies revealed that this interaction is highly conserved throughout the steroid hormone receptor family and functions as a key regulator of steroid hormone receptor sensitivity and specificity. Here, we review the contribution of helix 3-helix 5 interaction to steroid hormone receptor activity, with an eye towards how this knowledge may aid in the creation of novel therapeutic agonists and antagonists.
通过其受体发挥作用的类固醇激素调节着正常体内平衡所需的多种生理过程。近年来，我们对这些激素如何与它们的受体相互作用的理解取得了巨大进展，使我们更接近定向药物设计的时代。我们之前描述了螺旋3和螺旋5之间一种新的分子内相互作用，这种相互作用导致了一种孟德尔形式的人类高血压。进一步的研究表明，这种相互作用在整个类固醇激素受体家族中高度保守，并作为类固醇激素受体敏感性和特异性的关键调节因子发挥作用。在这里，我们回顾螺旋3-螺旋5相互作用对类固醇激素受体活性的贡献，着眼于这些知识如何有助于开发新型治疗激动剂和拮抗剂。
