Catalysis and Electron Transfer in Deâ
Novo Designed Helical Scaffolds.
Angew Chem Int Ed Engl
; 59(20): 7678-7699, 2020 05 11.
Article
em En
| MEDLINE
| ID: mdl-31441170
ABSTRACT
The relationship between protein structure and function is one of the greatest puzzles within biochemistry. Deâ
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 deâ
novo metalloproteins within alpha-helical scaffolds. Examples of successful designs include those with carbonic anhydrase or nitrite reductase activity by incorporating a ZnHis3 or CuHis3 site, or that recapitulate the spectroscopic properties of unique electron-transfer sites in cupredoxins (CuHis2 Cys) or rubredoxins (FeCys4 ). 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
/
Metaloproteínas
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos