Probing the Function of the Tyr-Cys Cross-Link in Metalloenzymes by the Genetic Incorporation of 3-Methylthiotyrosine

摘要

The thioether-bonded tyrosine-cysteine cofactor (Tyr-Cys, Scheme 1 A) is ubiquitous for diverse metalloenzymes, including the copper-dependent galactoase oxidase (GO) and glyoxal oxidase, iron-dependent cysteine dioxygenase (CDO), siroheme- and [Fe4S4]-dependent sulfite reductase (NirA), and T. nitratireducens cytochrome c nitrite reductase (TvNiR) (Supporting Information, Figures S4-S7). In all of the aforementioned enzymes, a covalent bond is formed autocatalytically between the C3 ring carbon atom of a tyrosine residue and the Sy atom of a neighboring cysteine residue, without requiring exogenous proteins (Scheme 1 A). Because of the fascinating chemistry and potential industrial applications of these enzymes, the functional significance of the essential Tyr-Cys cofactor has been intensively investigated by synthetic chemists, physical chemists, enzymologists, and structure biologists, and tremendous progress has been made in this area.