Fernández Ariel, Crespo Alejandro
Department of Bioengineering, Rice University, Houston, TX 77005, USA.
Chem Soc Rev. 2008 Nov;37(11):2373-82. doi: 10.1039/b804150b. Epub 2008 Sep 15.
In this tutorial review we survey the concept of protein wrapping from a physico-chemical perspective. Wrapping is introduced as an indicator of the packing quality of protein structure. Thus, while a well-wrapped protein is sustainable in isolation, a poorly wrapped protein is reliant on binding partnerships to maintain its structural integrity. At a local level, wrapping is indicative of the extent of solvent exposure of the amide-carbonyl hydrogen bonds of the protein backbone. Poorly wrapped hydrogen bonds, the so-called dehydrons, are shown to represent structural vulnerabilities. These singularities are sticky, hence promoters of protein associations. We also focus on severely under-wrapped protein structures that belong to an order/disorder twilight. Such proteins are shown to be prone to aggregate. Finally, we survey the recent exploitation of dehydrons as targetable features to promote specificity in drug-based cancer therapy. Dehydrons prove to be valuable targets to reduce side effects and enhance drug safety.
在本教程综述中，我们从物理化学角度审视蛋白质包裹的概念。包裹被引入作为蛋白质结构堆积质量的一个指标。因此，虽然包裹良好的蛋白质在孤立状态下是可持续的，但包裹不佳的蛋白质则依赖于结合伙伴关系来维持其结构完整性。在局部层面，包裹表明了蛋白质主链酰胺-羰基氢键的溶剂暴露程度。包裹不佳的氢键，即所谓的脱水子，被证明代表结构脆弱性。这些奇点具有粘性，因此是蛋白质缔合的促进剂。我们还关注属于有序/无序过渡态的严重包裹不足的蛋白质结构。此类蛋白质被证明易于聚集。最后，我们综述了最近将脱水子作为可靶向特征加以利用，以促进基于药物的癌症治疗的特异性。事实证明，脱水子是减少副作用和提高药物安全性的有价值靶点。
