Naturally occurring circular proteins: distribution, biosynthesis and evolution

Naturally occurring circular proteins: distribution, biosynthesis and evolution
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DOI:
10.1039/c0ob00139b
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发表时间:
2010-01-01
影响因子:
3.2
通讯作者:
Craik, David J.
Craik, David J.
中科院分区:
化学3区
文献类型:
--
作者:
Cascales, Laura;Craik, David J.

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环状蛋白,即,在过去的15年里,在细菌、植物、真菌和动物中发现了具有由连续和无缝的氨基酸环组成的骨架的蛋白质。它们在表达它们的生物体中起防御工具的作用,并且非常稳定。环肽是已知的最大的环状蛋白家族,并且由紫罗兰科(Violaceae)(紫罗兰)、茜草科(Rubiaceae)(咖啡)和葫芦科(Cucurbitaceae)(葫芦科)的植物表达,其中它们在植物防御昆虫捕食中起作用。到目前为止,在细菌或动物中环肽的例子较少,但我们认为环肽是一种未被发现的分子,在不久的将来会发现更多。人们对理解环状蛋白质的环化机制以及环状骨架在定义结构和活性中的作用非常感兴趣。在这篇评论中,家庭的核糖体合成的环状蛋白质报告的日期和他们的共同特点进行了检查,提供有关其分布,生物合成和进化的信息。环状蛋白质的不寻常结构赋予它们高稳定性,并使它们作为药物设计的支架非常有趣,这导致了线性蛋白质的重新设计以稳定它们并将它们用于此类应用。
Circular proteins, i.e., proteins with a backbone comprised of a continuous and seamless circle of amino acids, have been discovered over the last 15 years in bacteria, plants, fungi and animals. They function as defence tools in the organisms in which they are expressed and are exceptionally stable. The cyclotides are the largest known family of circular proteins and are expressed by plants of the Violaceae (violet), Rubiaceae (coffee) and Cucurbitaceae (cucurbit) families, where they have a role in plant defence against insect predation. So far there are fewer examples of cyclic peptides in bacteria or animals but we suggest that cyclic peptides are an underdiscovered class of molecules and that many more will be discovered in the near future. There is much interest in understanding the mechanism of cyclization of circular proteins and the role of the cyclic backbone in defining structure and activity. In this review, the families of ribosomally synthesized cyclic proteins reported to date are described and their common features are examined, providing information on their distribution, biosynthesis and evolution. The unusual structure of circular proteins confers them with high stability, and makes them very interesting as scaffolds for drug design, and this has led to the re-engineering of linear proteins to stabilise them and use them for such applications.