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首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >Homology modelling of the ligand binding domain of mineralocorticoid receptor: close structural kinship with glucocorticoid receptor ligand binding domain and their similar binding mode with DOC (de-oxy corticosterone).
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Homology modelling of the ligand binding domain of mineralocorticoid receptor: close structural kinship with glucocorticoid receptor ligand binding domain and their similar binding mode with DOC (de-oxy corticosterone).

机译：盐皮质激素受体配体结合结构域的同源性建模：与糖皮质激素受体配体结合结构域的紧密结构亲缘关系以及与DOC（脱氧皮质酮）的相似结合方式。

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摘要

Mineralocorticoids play a major role in regulating sodium and potassium homeostasis and also contribute to the control of blood pressure and in some physiological disorders. The physiological effects of this class of corticosteroids are mediated by ligand-induced nuclear transcription factor, the mineralocorticoid receptor(MR) / glucocorticoid receptor(GR), a member of the steroid / nuclear receptor superfamily. Although the MR interacts with both glucocorticoids and mineralocorticoids, the GR interacts specifically with glucocorticoids. The three dimensional structure of progesterone complexed to its receptor revealed in X-ray diffraction method is utilised to develop a homology model of human mineralocorticoid receptor ligand binding domain (hMR LBD) in a similar fashion as mouse GR LBD was developed previously. The secondary structure of hMR LBD contains eleven helices, eight turns and four sheets. This receptor contains a long helix, H9, with thirty four residues. The 12-residue C-terminal extension (residues 973-984) of hMR LBD, which is essential for hormone binding, is tightly fixed in position by an antiparallel b-sheet interaction. The three dimensional model reveals two polar sites located at the extremities of the elongated hydrophobic ligand-binding pocket (LBP). De-oxy corticosterone (DOC) is docked to the LBs of both hMR LBD and mGR LBD. The difference accessible surface area (DASA) study revealed the interaction zones of both the receptors in complex with DOC. Observations relating to the native and complex proteins revealed a close structural kinship between hMR LBD and mGR LBD.
机译：盐皮质激素在调节钠和钾稳态中起主要作用，并且还有助于控制血压和某些生理疾病。这类皮质类固醇的生理作用是由配体诱导的核转录因子介导的盐皮质激素受体（MR）/糖皮质激素受体（GR）（类固醇/核受体超家族成员）介导的。尽管MR与糖皮质激素和盐皮质激素相互作用，但GR与糖皮质激素特异性相互作用。利用X射线衍射方法揭示的与其受体复合的孕酮的三维结构，以与以前开发的小鼠GR LBD相似的方式开发人盐皮质激素受体配体结合域（hMR LBD）的同源性模型。 hMR LBD的二级结构包含11个螺旋，8个匝和4个薄片。该受体包含一个长螺旋H9，带有34个残基。 hMR LBD的12个残基的C末端延伸（残基973-984）对激素结合至关重要，它通过反平行的b-sheet相互作用紧密固定在位置上。三维模型揭示了两个极性位点，位于伸长的疏水性配体结合袋（LBP）的末端。脱氧皮质酮（DOC）与hMR LBD和mGR LBD的LB对接。差异可及表面积（DASA）研究揭示了两种受体与DOC形成复合物的相互作用区域。有关天然蛋白和复杂蛋白的观察表明，hMR LBD和mGR LBD之间具有紧密的结构亲缘关系。

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