3 publications

3 publications

Catalytic Efficiency of Designed Catalytic Proteins

Review

DeGrado, W.F.; Korendovych, I.V.

Curr. Opin. Struct. Biol. 2014, 27, 113-121, 10.1016/j.sbi.2014.06.006

The de novo design of catalysts that mimic the affinity and specificity of natural enzymes remains one of the Holy Grails of chemistry. Despite decades of concerted effort we are still unable to design catalysts as efficient as enzymes. Here we critically evaluate approaches to (re)design of novel catalytic function in proteins using two test cases: Kemp elimination and ester hydrolysis. We show that the degree of success thus far has been modest when the rate enhancements seen for the designed proteins are compared with the rate enhancements by small molecule catalysts in solvents with properties similar to the active site. Nevertheless, there are reasons for optimism: the design methods are ever improving and the resulting catalyst can be efficiently improved using directed evolution.


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Design of Artificial Enzymes by Supramolecular Strategies

Review

Liu, J.

Curr. Opin. Struct. Biol. 2018, 51, 19-27, 10.1016/j.sbi.2018.02.003

Enzymes are biomacromolecules with three-dimensional structures composed of peptide polymers via supramolecular interactions. Owing to the incredible catalytic efficiency and unique substrate selectivity, enzymes arouse considerable attention. To rival natural enzymes, various artificial enzymes have been developed over the last decades. Since supramolecular interactions play important roles in both substrate recognition and the process of enzymatic catalysis, designing artificial enzymes using supramolecular strategies is undoubtedly significant. Here we discuss the recent advances in constructing artificial enzymes using supramolecular platforms.


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The Ascent of Man(Made Oxidoreductases)

Review

Anderson, J.L.R.

Curr. Opin. Struct. Biol. 2018, 51, 149-155, 10.1016/j.sbi.2018.04.008

Though established 40 years ago, the field of de novo protein design has recently come of age, with new designs exhibiting an unprecedented level of sophistication in structure and function. With respect to catalysis, de novo enzymes promise to revolutionise the industrial production of useful chemicals and materials, while providing new biomolecules as plug-and-play components in the metabolic pathways of living cells. To this end, there are now de novo metalloenzymes that are assembled in vivo, including the recently reported C45 maquette, which can catalyse a variety of substrate oxidations with efficiencies rivalling those of closely related natural enzymes. Here we explore the successful design of this de novo enzyme, which was designed to minimise the undesirable complexity of natural proteins using a minimalistic bottom-up approach.


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