The ascent of man(made oxidoreductases)

Grayson, Katie J.; Anderson, J. L. Ross

doi:10.1016/j.sbi.2018.04.008

Cited by 26 publications

(22 citation statements)

References 73 publications

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“…Introduction of a flexible Cys containing linker allowed for further stabilization of the structure, effectively creating a helix–loop–helix motif (Robertson et al ., 1994). The original designs have been elaborated by Dutton, Moser, Gibney, Anderson, and coworkers to include complex single-chain topologies that allowed sequence diversification and recombinant expression (Grayson and Anderson, 2018). The simple geometry of maquettes (Fig.…”

Section: Computational Design Guided By Fundamental Physicochemical Pmentioning

confidence: 99%

De novoprotein design, a retrospective

Korendovych

DeGrado

2020

Quart. Rev. Biophys.

189

179

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Proteins are molecular machines whose function depends on their ability to achieve complex folds with precisely defined structural and dynamic properties. The rational design of proteins from first-principles, or de novo, was once considered to be impossible, but today proteins with a variety of folds and functions have been realized. We review the evolution of the field from its earliest days, placing particular emphasis on how this endeavor has illuminated our understanding of the principles underlying the folding and function of natural proteins, and is informing the design of macromolecules with unprecedented structures and properties. An initial set of milestones in de novo protein design focused on the construction of sequences that folded in water and membranes to adopt folded conformations. The first proteins were designed from first-principles using very simple physical models. As computers became more powerful, the use of the rotamer approximation allowed one to discover amino acid sequences that stabilize the desired fold. As the crystallographic database of protein structures expanded in subsequent years, it became possible to construct proteins by assembling short backbone fragments that frequently recur in Nature. The second set of milestones in de novo design involves the discovery of complex functions. Proteins have been designed to bind a variety of metals, porphyrins, and other cofactors. The design of proteins that catalyze hydrolysis and oxygen-dependent reactions has progressed significantly. However, de novo design of catalysts for energetically demanding reactions, or even proteins that bind with high affinity and specificity to highly functionalized complex polar molecules remains an importnant challenge that is now being achieved. Finally, the protein design contributed significantly to our understanding of membrane protein folding and transport of ions across membranes. The area of membrane protein design, or more generally of biomimetic polymers that function in mixed or non-aqueous environments, is now becoming increasingly possible.

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Section: Computational Design Guided By Fundamental Physicochemical Pmentioning

confidence: 99%

De novoprotein design, a retrospective

Korendovych

DeGrado

2020

Quart. Rev. Biophys.

189

179

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“…Extensive progress in protein design and engineering enables the construction of artificial metalloenzymes showing efficiency and substrate diversity beyond those of natural systems [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Heme-containing enzymes active in oxidation chemistry are a fascinating source of inspiration for researchers [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Artificial Heme Enzymes for the Construction of Gold-Based Biomaterials

Zambrano

Ruggiero

Malafronte

et al. 2018

IJMS

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Many efforts are continuously devoted to the construction of hybrid biomaterials for specific applications, by immobilizing enzymes on different types of surfaces and/or nanomaterials. In addition, advances in computational, molecular and structural biology have led to a variety of strategies for designing and engineering artificial enzymes with defined catalytic properties. Here, we report the conjugation of an artificial heme enzyme (MIMO) with lipoic acid (LA) as a building block for the development of gold-based biomaterials. We show that the artificial MIMO@LA can be successfully conjugated to gold nanoparticles or immobilized onto gold electrode surfaces, displaying quasi-reversible redox properties and peroxidase activity. The results of this work open interesting perspectives toward the development of new totally-synthetic catalytic biomaterials for application in biotechnology and biomedicine, expanding the range of the biomolecular component aside from traditional native enzymes.

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“…C45 has been presented by the Anderson group as a workhorse for functionality integration, showcasing catalytic activity without a specific active center. 34,105…”

Section: De Novo Scaffold Designmentioning

confidence: 99%

Step‐by‐step design of proteins for small molecule interaction: A review on recent milestones

2021

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Protein design is the field of synthetic biology that aims at developing de novo custom-made proteins and peptides for specific applications. Despite exploring an ambitious goal, recent computational advances in both hardware and software technologies have paved the way to high-throughput screening and detailed design of novel folds and improved functionalities. Modern advances in the field of protein design for small molecule targeting are described in this review, organized in a step-by-step fashion: from the conception of a new or upgraded active binding site, to scaffold design, sequence optimization, and experimental expression of the custom protein. In each step, contemporary examples are described, and state-of-the-art software is briefly explored.

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The ascent of man(made oxidoreductases)

Abstract: HighlightsHere we highlight our recent advances in de novo enzyme design.Heme C-binding maquettes with minimal complexity serve as promiscuous and efficient enzymes.Well-defined substrate binding sites are possibly not required for efficient oxidoreductase catalysis.

Cited by 26 publications

References 73 publications

De novoprotein design, a retrospective

De novoprotein design, a retrospective

Artificial Heme Enzymes for the Construction of Gold-Based Biomaterials

Step‐by‐step design of proteins for small molecule interaction: A review on recent milestones

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