Rational design of metalloenzymes: From single to multiple active sites

Abstract

Artificial metalloenzymes combine the advantages of both natural enzymes and chemically synthesized models, which have achieved significant progress in the last decade. This review summarizes the recent achievements in rational design of metalloenzymes from single to multiple active sites in natural or de novo protein scaffolds, with a diverse range of functionalities, even beyond those of natural metalloenzymes. These achievements include construction of mononuclear active site by metal substitution or incorporation, design of homo-or hetero-dinuclear site, introduction of Fe-sulfur or other metal clusters, reconstitution of metallo-porphyrins or other metal complexes, and design of dual or multiple active sites in single, dimeric proteins, de novo proteins, protein-protein interfaces, as well as protein oligomers and polymers. Other new trends in recent designs are also discussed. The progress not only elucidates the structural and functional relationship of natural metalloenzymes, but also provides practical clues for design of advanced artificial metalloenzymes with potential applications.

Uranyl Binding to Proteins and Structural-Functional Impacts

“…These advances shed light on the structure-function relationship of proteins, especially for metalloproteins, as impacted by uranyl-protein interactions. It is desired to seek approaches for biological remediation of uranyl ions, and ultimately make a full use of the double-edged sword of uranium.Proteins, especially for metalloproteins, play vital roles in supporting life, including electron-transfer, O 2 -binding and delivery, and catalysis, etc [11][12][13][14][15][16][17][18]. To date, a plenitude of proteins have been shown to interact with UO 2 2+ , such as proteins in blood (human serum albumin, HSA; transferrin, Tf;hemoglobin, Hb), proteins involved in bone growth (osteopontin, OPN; fetuin-A), and the intracellar proteins (metallothionein, MT; cytochromes b 5 /c; Cyt b 5 /c; calmodulin, CaM), etc [19].…”

Nitrite Reduction in Aqueous Solution Mediated by Amavadin Homologues: N2O Formation and Water Oxidation

“…Various fungi, including A. muscaria,a lso contribute to the nitrogen cycle with nitrite as possible metabolic substrate. Additionally,r ational design based on metallobiomolecules [62][63][64] hasb een employed for as imilar purpose. [21] Despite such great importance,t he chemical homogeneous reduction of nitrites by inorganic transition metals and internal transition-metal compounds has rarely been investigated.M ost studies focusedo ni ron [33][34][35][36][37][38][39][40][41][42][43][44][45] or copper [46][47][48][49][50][51][52] complexes that mimicked nitrite reductases.H owever,N O 2 À reduction with Ru, [53] Mo, [54][55][56] Ti,C r, [56] Co [57][58][59] andU [60] was also reported.…”

Streptavidin as a Scaffold for Light‐Induced Long‐Lived Charge Separation

“…[2][3][4][5] For this purpose, covalento r supramolecular assembly of an electron acceptor (A), an electron donor (D), and ap hotosensitizer (PS) affords an artificial triad A-PS-D. [6,7] Upon photochemical irradiation, the excited state A-PS*-D can reactt oa fford the corresponding( transient) charge-separated speciesA À -PS-D + .I nabiomimetic spirit, we set out to exploit ap rotein scaffold to positiona ll three components of an artificial triad. There are few examples of artificiald yads embedded within proteins or peptides; [8][9][10][11][12][13][14][15][16] but, to the best of our knowledge, artificial intramolecular triads relying on ap rotein scaffold have been unexplored.…”