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http://hdl.handle.net/2445/127866
Title: | Structure of the Reduced Copper Active Site in Pre-Processed Galactose Oxidase: Ligand Tuning for One-Electron O2 Activation in Cofactor Biogenesis |
Author: | Cowley, Ryan E. Cirera Fernández, Jordi Qayyum, Munzarin F. Rokhsana, Dalia Hedman, Britt Hodgson, Keith O. Dooley, David M. Solomon, Edward I. |
Keywords: | Enzims Transport d'electrons Catàlisi Enzymes Electron transport Catalysis |
Issue Date: | 14-Sep-2016 |
Publisher: | American Chemical Society |
Abstract: | Galactose oxidase (GO) is a copper-dependent enzyme that accomplishes 2e- substrate oxidation by pairing a single copper with an unusual cysteinylated tyrosine (Cys-Tyr) redox cofactor. Previous studies have demonstrated that the post-translational biogenesis of Cys-Tyr is copper- and O2-dependent, resulting in a self-processing enzyme system. To investigate the mechanism of cofactor biogenesis in GO, the active-site structure of Cu(I)-loaded GO was determined using X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectroscopy, and density-functional theory (DFT) calculations were performed on this model. Our results show that the active-site tyrosine lowers the Cu potential to enable the thermodynamically unfavorable 1e- reduction of O2, and the resulting Cu(II)-O2¿- is activated toward H atom abstraction from cysteine. The final step of biogenesis is a concerted reaction involving coordinated Tyr ring deprotonation where Cu(II) coordination enables formation of the Cys-Tyr cross-link. These spectroscopic and computational results highlight the role of the Cu(I) in enabling O2 activation by 1e- and the role of the resulting Cu(II) in enabling substrate activation for biogenesis. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1021/jacs.6b05792 |
It is part of: | Journal of the American Chemical Society, 2016, vol. 138, num. 40, p. 13219-13229 |
URI: | http://hdl.handle.net/2445/127866 |
Related resource: | https://doi.org/10.1021/jacs.6b05792 |
ISSN: | 0002-7863 |
Appears in Collections: | Articles publicats en revistes (Química Inorgànica i Orgànica) |
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