| Autor: |
Reig AJ; Department of Biochemistry & Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. areig@ursinus.edu, Pires MM, Snyder RA, Wu Y, Jo H, Kulp DW, Butch SE, Calhoun JR, Szyperski T, Solomon EI, DeGrado WF |
| Jazyk: |
angličtina |
| Zdroj: |
Nature chemistry [Nat Chem] 2012 Nov; Vol. 4 (11), pp. 900-6. Date of Electronic Publication: 2012 Sep 23. |
| DOI: |
10.1038/nchem.1454 |
| Abstrakt: |
De novo proteins provide a unique opportunity to investigate the structure-function relationships of metalloproteins in a minimal, well-defined and controlled scaffold. Here, we describe the rational programming of function in a de novo designed di-iron carboxylate protein from the Due Ferri family. Originally created to catalyse the O(2)-dependent, two-electron oxidation of hydroquinones, the protein was reprogrammed to catalyse the selective N-hydroxylation of arylamines by remodelling the substrate access cavity and introducing a critical third His ligand to the metal-binding cavity. Additional second- and third-shell modifications were required to stabilize the His ligand in the core of the protein. These structural changes resulted in at least a 10(6)-fold increase in the relative rate between the arylamine N-hydroxylation and hydroquinone oxidation reactions. This result highlights the potential for using de novo proteins as scaffolds for future investigations of the geometric and electronic factors that influence the catalytic tuning of di-iron active sites. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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