Molecular recognition of insulin by a synthetic receptor.
Molecular recognition of insulin by a synthetic receptor.
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DOI：
10.1021/ja201581x
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发表时间：
2011-06-15
影响因子：
15
通讯作者：
Urbach, Adam R.
中科院分区：
文献类型：
--
作者：
Chinai, Jordan M.;Taylor, Alexander B.;Ryno, Lisa M.;Hargreaves, Nicholas D.;Morris, Christopher A.;Hart, P. John;Urbach, Adam R.
与所需蛋白质紧密且有选择性结合的分子的发现继续推动化学和生物学界面的创新。本文报道了人胰岛素与合成受体瓜环（Q7）的体外结合。等温滴定量热法和荧光光谱实验表明，Q7与胰岛素结合的平衡结合常数为1.5 × 106 M-1，与大得多但缺乏N-末端芳香残基的蛋白质相比具有50-100倍的选择性，与缺乏N-末端苯丙氨酸（Phe）残基的胰岛素变体相比具有>1000倍的选择性。Q7·胰岛素复合物的晶体结构显示，结合发生在N-末端Phe残基处，并且N-末端展开以实现结合。这些发现表明，位点选择性识别是基于蛋白质末端固有的特性，包括末端残基呈现的独特化学表位，以及末端展开的更大自由度，就像一个线团的末端一样，以适应结合。从短肽的研究中准确预测了胰岛素识别，并证实了通过靶向末端来识别蛋白质的方法。
The discovery of molecules that bind tightly and selectively to desired proteins continues to drive innovation at the interface of chemistry and biology. This paper describes the binding of human insulin by the synthetic receptor cucurbit[7]uril (Q7) in vitro. Isothermal titration calorimetry and fluorescence spectroscopy experiments show that Q7 binds to insulin with an equilibrium association constant of 1.5 × 106 M-1 and with 50-100-fold selectivity versus proteins that are much larger but lack an N-terminal aromatic residue, and >1000-fold selectivity versus an insulin variant lacking the N-terminal phenylalanine (Phe) residue. The crystal structure of the Q7•insulin complex shows that binding occurs at the N-terminal Phe residue and that the N-terminus unfolds to enable binding. These findings suggest that site-selective recognition is based on the properties inherent to a protein terminus, including the unique chemical epitope presented by the terminal residue and the greater freedom of the terminus to unfold, like the end of a ball of string, to accommodate binding. Insulin recognition was predicted accurately from studies on short peptides and exemplifies an approach to protein recognition by targeting the terminus.
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影响因子：
15
作者：
Heitmann, Lisa M.;Taylor, Alexander B.;Urbach, Adam R.
通讯作者：
Urbach, Adam R.
DOI：
10.1007/s10847-008-9464-y
发表时间：
2008-12-01
影响因子：
2.3
作者：
Rajgariah, P.;Urbach, A. R.
通讯作者：
Urbach, A. R.
影响因子：
15
作者：
Rekharsky, Mikhail V.;Yamamura, Hatsuo;Inoue, Yoshihisa
通讯作者：
Inoue, Yoshihisa
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
4.9
作者：
Isaacs, Lyle
通讯作者：
Isaacs, Lyle