MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, China.
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
Nat Commun. 2022 Aug 16;13(1):4816. doi: 10.1038/s41467-022-32454-2.
Nature programs the structural folding of an enzyme that allows its on-demand biofunctionality; however, it is still a long-standing challenge to manually modulate an enzyme's conformation. Here, we design an exogenous hydrogen-bonded organic framework to modulate the conformation of cytochrome c, and hence allow non-native bioactivity for the enzyme. The rigid hydrogen-bonded organic framework, with net-arranged carboxylate inner cage, is in situ installed onto the native cytochrome c. The resultant hydrogen-bonded nano-biointerface changes the conformation to a previously not achieved catalase-like species within the reported cytochrome c-porous organic framework systems. In addition, the preserved hydrogen-bonded organic framework can stabilize the encapsulated enzyme and its channel-like pores also guarantee the free entrance of catalytic substrates. This work describes a conceptual nanotechnology for manoeuvring the flexible conformations of an enzyme, and also highlights the advantages of artificial hydrogen-bonded scaffolds to modulate enzyme activity.
自然程序设计了一种酶的结构折叠，使其具有按需的生物功能性；然而，人工调节酶的构象仍然是一个长期存在的挑战。在这里，我们设计了一种外源性氢键有机框架来调节细胞色素 c 的构象，从而为酶赋予非天然的生物活性。刚性氢键有机框架，具有净排列的羧酸内笼，原位安装在天然细胞色素 c 上。所得的氢键纳米生物界面将构象改变为之前在报道的细胞色素 c-多孔有机框架系统中未达到的过氧化物酶类似物。此外，保留的氢键有机框架可以稳定包封的酶，其通道样孔也保证了催化底物的自由进入。这项工作描述了一种用于操纵酶的柔性构象的概念性纳米技术，并强调了人工氢键支架调节酶活性的优势。
