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2016-09-14

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/127866

Structure of the Reduced Copper Active Site in Pre-Processed Galactose Oxidase: Ligand Tuning for One-Electron O2 Activation in Cofactor Biogenesis

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https://doi.org/10.1021/jacs.6b05792

Resum

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.

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Enzims, Transport d'electrons, Catàlisi

Matèries (anglès)

Enzymes, Electron transport, Catalysis

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Articles publicats en revistes (Química Inorgànica i Orgànica)

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COWLEY, Ryan e., CIRERA FERNÁNDEZ, Jordi, QAYYUM, Munzarin f., ROKHSANA, Dalia, HEDMAN, Britt, HODGSON, Keith o., DOOLEY, David m., SOLOMON, Edward i.. Structure of the Reduced Copper Active Site in Pre-Processed Galactose Oxidase: Ligand Tuning for One-Electron O2 Activation in Cofactor Biogenesis. _Journal of the American Chemical Society_. 2016. Vol. 138, núm. 40, pàgs. 13219-13229. [consulta: 30 de gener de 2026]. ISSN: 0002-7863. [Disponible a: https://hdl.handle.net/2445/127866]

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