Abstract
Metalloproteins and metalloenzymes play important roles in biological systems by using the limited metal ions, complexes, and clusters that are associated with the protein matrix. The design of artificial metalloproteins and metalloenzymes not only reveals the structure and function relationship of natural proteins, but also enables the synthesis of artificial proteins and enzymes with improved properties and functions. Acknowledging the progress in rational design from single to multiple active sites, this review focuses on recent achievements in the design of artificial metalloproteins and metalloenzymes with metal clusters, including zinc clusters, cadmium clusters, iron–sulfur clusters, and copper–sulfur clusters, as well as noble metal clusters and others. These metal clusters were designed in both native and de novo protein scaffolds for structural roles, electron transfer, or catalysis. Some synthetic metal clusters as functional models of native enzymes are also discussed. These achievements provide valuable insights for deep understanding of the natural proteins and enzymes, and practical clues for the further design of artificial enzymes with functions comparable or even beyond those of natural counterparts.
Highlights
Metalloproteins and metalloenzymes play important roles in biological systems, including electron transfer, O2 binding and delivery, and catalysis, etc. [1,2,3,4,5,6,7,8,9,10,11]
The cofactor or prosthetic group of native metalloproteins/metalloenzymes are made of about 14 metal ions, and several types of metal complexes or metal clusters [4,5,10], which may limit the functionalities of native metalloenzymes
Metalloproteins and witheither diverse metalclusters have rationally designedartificial in recent years, in which themetalloenzymes clustersare formed in the protein pocket, been rationally designed in recent years, in which the clustersare formed either in the protein between the interface of protein dimers, trimers, and oligomers, or within the scaffold of de novo pocket, between theAs interface protein1,dimers, trimers, and oligomers, or within the scaffold ofnot de designed proteins
Summary
Metalloproteins and metalloenzymes play important roles in biological systems, including electron transfer, O2 binding and delivery, and catalysis, etc. [1,2,3,4,5,6,7,8,9,10,11]. In the design of artificial metalloproteins and metalloenzymes, many strategies have been developed, such as redesign of the active metal site by fine-tuning the cofactor–protein interactions through site/loop-directed mutagenesis [30,31,32], the design of new metal-binding sites [33,34,35,36,37,38], the incorporation of unnatural amino acids and non-native cofactors into native or de novo protein scaffolds [20,25,39,40,41], and the directed evolution of metalloenzymes [23,42], as well as the use of post-translational modifications (PTMs) [43,44,45,46,47,48,49,50] Other materials such as nanoparticles and hydrogels have been used for the design of enzyme mimics [51,52,53].
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