Proteins from an unevolved library of de novo designed sequences bind a range of small molecules.
Proteins from an unevolved library of de novo designed sequences bind a range of small molecules.
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DOI：
10.1021/sb200018e
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发表时间：
2012-04-20
影响因子：
4.7
通讯作者：
Hecht, Michael H.
中科院分区：
文献类型：
--
作者：
Cherny, Izhack;Korolev, Maria;Koehler, Angela N.;Hecht, Michael H.
大量从头设计的蛋白质的可用性为利用新的大分子合成生物功能提供了新的机会。这些新功能中的许多都需要与小分子结合。结合小分子的能力是不是只有在生物选择或计算设计的反应中才出现的特性？或者，小分子结合是折叠蛋白质的一种特性，在未进化序列的集合中很容易发生吗？这些问题可以通过评估从头蛋白质的结合潜力来解决，这些从头蛋白质被设计成折叠成稳定结构，但在某种意义上它们是“幼稚的”，即它们（i）与天然蛋白质没有显著的序列相似性，并且（ii）既没有被选择也没有被设计成结合小分子。我们从设计折叠成4-螺旋束的序列库中选择了三种天然蛋白质，并筛选了与小分子微阵列上显示的10，000种化合物的结合。鉴定了几种结合剂，并通过一系列生物物理测定表征结合。令人惊讶的是，尽管三种从头蛋白彼此相似，但它们表现出选择性配体结合。这些发现证明了新型蛋白质在分子识别方面的潜力，并对合成生物学的一系列应用具有重要意义。
The availability of large collections of de novo designed proteins presents new opportunities to harness novel macromolecules for synthetic biological functions. Many of these new functions will require binding to small molecules. Is the ability to bind small molecules a property that arises only in response to biological selection or computational design? Or alternatively, is small molecule binding a property of folded proteins that occurs readily amidst collections of unevolved sequences? These questions can be addressed by assessing the binding potential of de novo proteins that are designed to fold into stable structures, but are “naïve” in the sense that they (i) share no significant sequence similarity with natural proteins, and (ii) were neither selected nor designed to bind small molecules. We chose three naïve proteins from a library of sequences designed to fold into 4-helix bundles, and screened for binding to 10,000 compounds displayed on small molecule microarrays. Several binders were identified, and binding was characterized by a series of biophysical assays. Surprisingly, despite the similarity of the three de novo proteins to one another, they exhibit selective ligand binding. These findings demonstrate the potential of novel proteins for molecular recognition, and have significant implications for a range of applications in synthetic biology.
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影响因子：
15
作者：
Chen J;Armstrong AH;Koehler AN;Hecht MH
通讯作者：
Hecht MH
影响因子：
8
作者：
Go, Abigail;Kim, Seho;Hecht, Michael H.
通讯作者：
Hecht, Michael H.
影响因子：
--
作者：
Bradner, James E.;McPherson, Olivia M.;Koehler, Angela N.
通讯作者：
Koehler, Angela N.
DOI：
10.1073/pnas.0506124102
发表时间：
2005-09-06
影响因子：
11.1
作者：
Bolon, DN;Grant, RA;Sauer, RT
通讯作者：
Sauer, RT
影响因子：
4.9
作者：
CHANG, FN;FLAKS, JG
通讯作者：
FLAKS, JG