Protein prosthesis: β-peptides as reverse-turn surrogates
Protein prosthesis: β-peptides as reverse-turn surrogates
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DOI：
10.1002/pro.2208
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发表时间：
2013-03-01
期刊：
影响因子：
8
通讯作者：
Raines, Ronald T.
中科院分区：
文献类型：
--
作者：
Arnold, Ulrich;Huck, Bayard R.;Raines, Ronald T.
非天然模块的引入可以对蛋白质的折叠/展开行为、构象稳定性和生物功能提供前所未有的控制。成功需要在自然环境中询问候选模块。此处，表达的蛋白质连接用于用合成的β二肽：2-高丙氨酸3-高丙氨酸取代牛胰腺核糖核酸酶（RNase A）中的反向转折。已知该片段采用非自然的回转构象，其中包含 10 元环氢键，但其供体受体模式与天然回转的 10 元环相反。 RNase A 变体具有完整的酶活性，但与天然 RNase A 相比，展开速度更快，并且构象稳定性降低。这些数据表明，在选择有益的回折替代物时，氢键模式值得仔细考虑。
The introduction of non-natural modules could provide unprecedented control over folding/unfolding behavior, conformational stability, and biological function of proteins. Success requires the interrogation of candidate modules in natural contexts. Here, expressed protein ligation is used to replace a reverse turn in bovine pancreatic ribonuclease (RNase A) with a synthetic -dipeptide: 2-homoalanine3-homoalanine. This segment is known to adopt an unnatural reverse-turn conformation that contains a 10-membered ring hydrogen bond, but one with a donoracceptor pattern opposite to that in the 10-membered rings of natural reverse turns. The RNase A variant has intact enzymatic activity, but unfolds more quickly and has diminished conformational stability relative to native RNase A. These data indicate that hydrogen-bonding pattern merits careful consideration in the selection of beneficial reverse-turn surrogates.