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The establishment of new enzymatic function in an existing scaffold is a great challenge for protein engineers. In previous work, a highly efficient artificial selenoenzyme with controllable activity was constructed, based on a Ca 2+ -responsive recoverin (Rn) protein. In this study, a design strategy combining docking, molecular dynamics, and MM-PBSA is presented, to predict the catalytically active site of glutathione peroxidase (GPx) on the allosteric domain of Rn. The energy contributions of the binding hot spot residues are evaluated further by energy decomposition analysis to determine the detailed substrate recognition mechanism of Rn, which provides clear guidance for artificial enzyme design for improved substrate binding (Michaelis-Menten constant, K m )., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A pH-responsive artificial selenoenzyme was constructed by reversible binding between organoselenium compound a1 nd CB[6] to form a pseudorotaxane-based molecular switch in response to pH stimuli. The glutathione peroxidase (GPx) activity of the artificial selenoenzyme can be switched on/off in a mild and body suitable environment between pH = 7 and pH = 6.

Signal transduction across lipid bilayers is of profound importance in biological processes. In biological systems, natural enzymes mediate biochemical effects by binding to substrates and facilitating the conversion of external signals into physiological responses. Sequential transmission of biological signals from one enzyme to the next promotes signal transduction with feedforward and feedback mechanisms. Reconstructing these processes in an artificial system provides potential applications and offers a new way to understand fundamental biological processes in depth. However, the design of artificial signal transduction systems regulated by artificial enzyme receptors in a predictable and intelligent manner remains a challenge. Herein, benefiting from the polarity-regulated characteristics of Se-containing compounds with artificial glutathione peroxidase (GPx) activity, we constructed an artificial transmembrane signaling receptor with a Se-containing GPx-like recognition head group, a membrane-anchoring group, and a pre-enzyme end group. The artificial supramolecular signal transduction system containing such signal transduction receptors extends the range of signaling systems based on enzyme regulation, which provides a new way to study natural signal processes in cells and artificially regulated biological processes. [ABSTRACT FROM AUTHOR]

The atomically monodispersed dual‐atom nanozyme not only possesses the advantages of homogeneous active centers and high atomic utilization efficiency but also exhibits amazing synergistic effect for higher catalytic activities than single‐atom nanozyme. However, how to construct dual‐atom nanozyme with multi‐enzyme cascade capacity for protecting against brain tissue damage is a great challenge. Herein, for coping with the secondary damage to brain tissue caused by the explosive generation of reactive oxygen species(ROS) during cerebral ischemia‐reperfusion, a multi‐enzyme cascade antioxidant system is constructed by encapsulating dual‐Fe‐atom nanozyme (Fe2NC) in a selenium‐containing MOF (Se‐MOF) shell layer. The designed dual‐Fe‐atom nanozyme exhibits higher superoxide dismutase‐like, catalase‐like, and even oxidase‐like activities than single‐atom Fe (Fe1NC) nanozyme, and moreover, the Se‐MOF shell layer not only acts as a glutathione peroxidase mimic, but also improves the stability and biocompatibility of the Fe2NC nanozyme obviously. The synergistic effect of Fe2NC has been demonstrated to be the main reason for the higher activity by density functional theory calculations. In vitro and in vivo results reveal that the multifunctional antioxidant Fe2NC@Se nanoparticles can counteract oxidative damage and inhibit neural apoptosis after cerebral ischemia‐reperfusion injury by effectively eliminating intracellular ROS and potentially inhibiting the ASK1/JNK apoptotic signaling pathway. [ABSTRACT FROM AUTHOR]

A supramolecular nanocapsule was constructed by the ternary host–guest complexation of azobenzene (Azo) and methylviologen (MV) to cucurbit[8]uril (CB[8]) and the subsequent self-assembly. The supramolecular nanocapsule with both glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities can mimic the intracellular enzymatic reactive oxygen species (ROS) defense system. [ABSTRACT FROM AUTHOR]