Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur 741246, India.
J Am Chem Soc. 2020 Mar 4;142(9):4098-4103. doi: 10.1021/jacs.9b13517. Epub 2020 Feb 24.
The binding pockets of extant enzymes feature precise positioning of amino acid residues that facilitate multiple complex transformations exploiting covalent and non-covalent interactions. Reversible covalent anchoring is extensively used as an efficient tool by Nature for activating modern enzymes such as esterases and dehydratases and also for proteins like opsins for the complex process of visual phototransduction. Here we construct paracrystalline amyloid surfaces through the self-propagation of short peptides which offer binding pockets exposed with arrays of imidazoles and lysines. As covalent catalysis is utilized by modern-day enzymes, these homogeneous amyloid nanotubes exploit Schiff imine formation via the exposed lysines to efficiently hydrolyze both activated and inactivated esters. Controls where lysines were mutated with charged residues accessed similar morphologies but did not augment the rate. The designed amyloid microphases thus foreshadow the generation of binding pockets of advanced proteins and have the potential to contribute to the development of functional materials.
现存酶的结合口袋具有精确定位的氨基酸残基，有利于利用共价和非共价相互作用进行多种复杂转化。可逆共价锚定被广泛用作自然界激活现代酶（如酯酶和脱水酶）以及视蛋白等蛋白质的有效工具，用于视觉光转导这一复杂过程。在这里，我们通过短肽的自我传播构建准晶态淀粉样表面，这些短肽提供了带有咪唑和赖氨酸阵列的暴露结合口袋。由于现代酶利用共价催化，这些均相淀粉样纳米管通过暴露的赖氨酸利用席夫碱形成来有效地水解激活和非激活的酯。赖氨酸被带电荷残基突变的对照实验获得了相似的形态，但没有提高反应速率。因此，设计的淀粉样微相预示着先进蛋白质结合口袋的产生，并有可能为功能材料的发展做出贡献。
