De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy.
De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy.
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DOI：
10.1038/nchembio.1966
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发表时间：
2016-01
影响因子：
14.8
通讯作者：
Baker D
中科院分区：
文献类型：
--
作者：
Huang PS;Feldmeier K;Parmeggiani F;Velasco DAF;Höcker B;Baker D
尽管努力超过25年，但在这里，DE NOK蛋白设计尚未成功实现TIM键在33个设计中，露出氢键在重复单元之间定义了链条寄存器的重要性请勿确定与已知的Tim-Barrel蛋白的序列相似性，并且灵敏的概况搜索搜索表明，该设计序列远离其他天然发生的Tim-Barrel超家族，这表明大自然仅对TIM可用的序列空间进行了采样-Barrel折叠的能力。
Despite efforts for over 25 years, de novo protein design has not succeeded in achieving the TIM-barrel fold. Here we describe the computational design of 4-fold symmetrical (β/α)8-barrels guided by geometrical and chemical principles. Experimental characterization of 33 designs revealed the importance of sidechain-backbone hydrogen bonding for defining the strand register between repeat units. The X-ray crystal structure of a designed thermostable 184-residue protein is nearly identical with the designed TIM-barrel model. PSI-BLAST searches do not identify sequence similarities to known TIM-barrel proteins, and sensitive profile-profile searches indicate that the design sequence is distant from other naturally occurring TIM-barrel superfamilies, suggesting that Nature has only sampled a subset of the sequence space available to the TIM-barrel fold. The ability to de novo design TIM-barrels opens new possibilities for custom-made enzymes.