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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Structural characterization of the PPIase domain of FKBP51, a cochaperone of human Hsp90.
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Structural characterization of the PPIase domain of FKBP51, a cochaperone of human Hsp90.

机译：PPIase域的结构特征cochaperone FKBP51的人类的一半。

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摘要

Steroid hormone receptors are key components of mammalian stress and sex hormone systems. Many of them rely on the Hsp90 chaperone system for full function and are further fine-tuned by Hsp90-associated peptidyl-prolyl isomerases such as FK506-binding proteins 51 and 52. FK506-binding protein 51 (FKBP51) has been shown to reduce glucocorticoid receptor signalling and has been genetically associated with human stress resilience and with numerous psychiatric disorders. The peptidyl-prolyl isomerase domain of FKBP51 contains a high-affinity binding site for the natural products FK506 and rapamycin and has further been shown to convey most of the inhibitory activity on the glucocorticoid receptor. FKBP51 has therefore become a prime new target for the treatment of stress-related affective disorders that could be amenable to structure-based drug design. Here, a series of high-resolution structures of the peptidyl-prolyl isomerase domain of FKBP51 as well as a cocrystal structure with the prototypic ligand FK506 are described. These structures provide a detailed picture of the drug-binding domain of FKBP51 and the molecular binding mode of its ligand as a starting point for the rational design of improved inhibitors.
机译：类固醇激素受体是关键组成部分哺乳动物的压力和性激素系统。他们依靠一半伴侣系统完整函数,进一步调整Hsp90-associated peptidyl-prolyl异构酶等51 FK506-binding蛋白质和52。51 FK506-binding蛋白质(FKBP51)已被证明减少糖皮质激素受体信号基因与人类相关的压力弹性和许多精神障碍。FKBP51包含一个高亲和性结合位点天然产物的吸收FK506和雷帕霉素进一步被证实转达的吗糖皮质激素抑制活动受体。与压力相关的治疗目标情感障碍可能经得起检验基于结构的药物设计。peptidyl-prolyl的高分辨率结构异构酶域FKBP51以及cocrystal结构与配位体吸收FK506被描述。FKBP51 drug-binding域和的照片其配体的分子绑定模式设计合理的起点改进的抑制剂。

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