Catalysis and Electron Transfer in De Novo Designed Helical Scaffolds.

Autor: Pinter TBJ; Department of Chemistry, University of Michigan, Ann Arbor, Michigan, 48109-1055, USA., Koebke KJ; Department of Chemistry, University of Michigan, Ann Arbor, Michigan, 48109-1055, USA., Pecoraro VL; Department of Chemistry, University of Michigan, Ann Arbor, Michigan, 48109-1055, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2020 May 11; Vol. 59 (20), pp. 7678-7699. Date of Electronic Publication: 2020 Mar 02.
DOI: 10.1002/anie.201907502
Abstrakt: 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.
(© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
Externí odkaz: