Gewirth D T, Sigler P B
Department of Molecular Biophysics and Biochemistry, Yale University New Haven, Connecticut 06510, USA.
Nat Struct Biol. 1995 May;2(5):386-94. doi: 10.1038/nsb0595-386.
Steroid receptors recognize bipartite targets composed of six base-pair half-sites. There are two canonical types of half-site which differ only in their central two base pairs. The crystal structure of an estrogen receptor-like DNA-binding domain bound to the wrong type of half-site (a glucocorticoid response element) reveals an interface that resembles the specific interfaces of the glucocorticoid receptor or estrogen receptor bound to their correct response elements. The underlying stereochemical defect that weakens the non-cognate interface is a difference in the helical geometry of the incorrect DNA half-site which prevents a side-chain contact and results in a gap which is filled by at least five additional fixed water sites, imposing a potential entropic burden on the stability of the interface.
类固醇受体识别由六个碱基对半位点组成的二分靶标。有两种典型的半位点类型，它们仅在中间的两个碱基对有所不同。与错误类型的半位点（糖皮质激素反应元件）结合的雌激素受体样DNA结合结构域的晶体结构揭示了一个界面，该界面类似于糖皮质激素受体或雌激素受体与其正确反应元件结合时的特定界面。削弱非同源界面的潜在立体化学缺陷是不正确的DNA半位点螺旋几何形状的差异，这阻止了侧链接触并导致一个间隙，该间隙由至少五个额外的固定水位点填充，给界面稳定性带来潜在的熵负担。
