3 years ago

Tyrosine or Tryptophan? Modifying a Metalloradical Catalytic Site by Removal of the Cys–Tyr Cross-Link in the galactose 6-oxidase homologue GlxA

Tyrosine or Tryptophan? Modifying a Metalloradical Catalytic Site by Removal of the Cys–Tyr Cross-Link in the galactose 6-oxidase homologue GlxA
Adalgisa Sinicropi, Riccardo Basosi, Amanda K. Chaplin, Jonathan A. R. Worrall, Dimitri A. Svistunenko, Caterina Bernini
The concerted redox action of a metal ion and an organic cofactor is a unique way to maximize the catalytic power of an enzyme. An example of such synergy is the fungal galactose 6-oxidase, which has inspired the creation of biomimetic copper oxidation catalysts. Galactose 6-oxidase and its bacterial homologue, GlxA, possess a metalloradical catalytic site that contains a free radical on a covalently linked Cys–Tyr and a copper atom. Such a catalytic site enables for the two-electron oxidation of alcohols to aldehydes. When the ability to form the Cys–Tyr in GlxA is disrupted, a radical can still be formed. Surprisingly, the radical species is not the Tyr residue but rather a copper second-coordination sphere Trp residue. This is demonstrated through the introduction of a new algorithm for Trp-radical EPR spectra simulation. Our findings suggest a new mechanism of free-radical transfer between aromatic residues and that the Cys–Tyr cross-link prevents radical migration away from the catalytic site. Breaking the bond is still radical: Copper radical oxidases contain an unusual Cys–Tyr redox cofactor capable of housing a stable protein radical required for their catalytic activity. Breaking the Cys–Tyr bond still yields a radical, surprisingly not on the Tyr but on the π-stacking Trp residue.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201701270

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