2 publications

2 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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Minimalist de Novo Design of Protein Catalysts

Review

Korendovych, I.V.

ACS Catal. 2019, 9, 9265-9275, 10.1021/acscatal.9b02509

The field of protein design has grown enormously in the past few decades. In this review, we discuss the minimalist approach to the design of artificial enzymes, in which protein sequences are created with the minimum number of elements for folding and function. This method relies on identifying starting points in catalytically inert scaffolds for active site installation. The progress of the field from the original helical assemblies of the 1980s to the more complex structures of the present day is discussed, highlighting the variety of catalytic reactions which have been achieved using these methods. We outline the strengths and weaknesses of the minimalist approaches, describe representative design cases, and put it in the general context of the de novo design of proteins.


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