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Catalysis and Electron Transfer in De Novo Designed Helical Scaffolds
Author(s) -
Pinter Tyler B. J.,
Koebke Karl J.,
Pecoraro Vincent L.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201907502
Subject(s) - metalloprotein , nitrite reductase , active site , chemistry , carbonic anhydrase , rational design , function (biology) , electron transfer , biochemistry , enzyme , combinatorial chemistry , nanotechnology , nitrate reductase , biology , materials science , microbiology and biotechnology , organic chemistry
The relationship between protein structure and function is one of the greatest puzzles within biochemistry. De novo metalloprotein design is a way to wipe the board clean and determine what is required to build in function from the ground up in an unrelated structure. This Review focuses on protein design efforts to create de novo metalloproteins within alpha‐helical scaffolds. Examples of successful designs include those with carbonic anhydrase or nitrite reductase activity by incorporating a ZnHis 3 or CuHis 3 site, or that recapitulate the spectroscopic properties of unique electron‐transfer sites in cupredoxins (CuHis 2 Cys) or rubredoxins (FeCys 4 ). This work showcases the versatility of alpha helices as scaffolds for metalloprotein design and the progress that is possible through careful rational design. Our studies cover the invariance of carbonic anhydrase activity with different site positions and scaffolds, refinement of our cupredoxin models, and enhancement of nitrite reductase activity up to 1000‐fold.