Department of Chemistry, Virginia Tech, Blacksburg, VA-24061, USA.
Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA-24061, USA.
Angew Chem Int Ed Engl. 2023 Jun 26;62(26):e202303755. doi: 10.1002/anie.202303755. Epub 2023 May 17.
We report three constitutionally isomeric tetrapeptides, each comprising one glutamic acid (E) residue, one histidine (H) residue, and two lysine (K ) residues functionalized with side-chain hydrophobic S-aroylthiooxime (SATO) groups. Depending on the order of amino acids, these amphiphilic peptides self-assembled in aqueous solution into different nanostructures:nanoribbons, a mixture of nanotoroids and nanoribbons, or nanocoils. Each nanostructure catalyzed hydrolysis of a model substrate, with the nanocoils exhibiting the greatest rate enhancement and the highest enzymatic efficiency. Coarse-grained molecular dynamics simulations, analyzed with unsupervised machine learning, revealed clusters of H residues in hydrophobic pockets along the outer edge of the nanocoils, providing insight for the observed catalytic rate enhancement. Finally, all three supramolecular nanostructures catalyzed hydrolysis of the l-substrate only when a pair of enantiomeric Boc-l/d-Phe-ONp substrates were tested. This study highlights how subtle molecular-level changes can influence supramolecular nanostructures, and ultimately affect catalytic efficiency.
我们报告了三种具有宪法结构异构体的四肽，每种都由一个谷氨酸（E）残基、一个组氨酸（H）残基和两个赖氨酸（K）残基组成，它们的侧链疏水 S-芳酰硫肟（SATO）基团被功能化。根据氨基酸的顺序，这些两亲肽在水溶液中自组装成不同的纳米结构：纳米带、纳米环和纳米带的混合物或纳米螺旋。每种纳米结构都催化了模型底物的水解，其中纳米螺旋表现出最大的速率增强和最高的酶效率。使用无监督机器学习分析的粗粒度分子动力学模拟揭示了纳米螺旋外边缘疏水口袋中 H 残基的簇，为观察到的催化速率增强提供了见解。最后，当一对对映体 Boc-l/d-Phe-ONp 底物进行测试时，这三种超分子纳米结构都仅催化 l-底物的水解。这项研究强调了微小的分子水平变化如何影响超分子纳米结构，并最终影响催化效率。
