Direct Spectroscopic Evidence for a High-Spin Fe(IV) Intermediate in Tyrosine Hydroxylase

• DOI: 10.1021/ja074446s
• Publication Date: 2007-08-23T12:00:50Z
• Authors: Bekir E. Eser; Eric W. Barr; Patrick A. Frantom; Lana Saleh; J. Martin Bollinger; Carsten Krebs; Paul F. Fitzpatrick
• Keywords: Spectroscopy, Mossbauer; Tyrosine 3-Monooxygenase; Iron; Hydroxylation; 01 natural sciences; Dihydroxyphenylalanine; 0104 chemical sciences

Tyrosine hydroxylase, a member of the aromatic amino acid hydroxylase family, uses a mononuclear Fe(II) and tetrahydropterin for hydroxylation of tyrosine to dihydroxyphenylalanine. Rapid-freeze quench Mossbauer spectroscopy has now provided direct evidence for the presence of an Fe(IV) intermediate in the reaction catalyzed by tyrosine hydroxylase. Rapid-quench techniques provide support for the kinetic competence of this species as the hydroxylating intermediate. This is the first direct evidence for a mononuclear Fe(IV) intermediate in an enzymatic aromatic hydroxylation reaction.