Reaction products and intermediates of tryptophan tryptophylquinone enzymes

Methylamine dehydrogenase and aromatic amine dehydrogenase each possess the tryptophan tryptophylquinone (TTQ) cofactor which catalyzes the oxidative deamination of primary amines and transfer of substrate-derived electrons t o type I copper proteins. The reaction steps and intermediates in the overa ll oxidation-reduction reactions catalyzed by these enzymes are described. An important feature of the reaction mechanism of TTQ-dependent amine dehyd rogenases is that the product of the reductive half-reaction is the reduced aminoquinol in which the substrate-derived amino group is covalently incor porated into the reduced TTQ cofactor. This has been proven by use of N-15 NMR spectroscopy to monitor the fate of nitrogen from N-15-labeled substrat e. This intermediate is significant because the covalent incorporation of N into the reduced TTQ has profound effects on the rates of electron transfe r and factors which regulate the electron transfer reactions from the reduc ed enzymes. Study of the oxidative half-reaction of methylamine dehydrogena se showed that incorporation of the substrate-derived amino group into TTQ caused this reaction to become gated by a proton transfer from the aminoqui nol, and revealed an important role for monovalent cations in the regulatio n of this reaction step. Analysis of monovalent cation-induced perturbation s of the absorption spectrum of TTQ-dependent enzymes has provided insight into the mechanism of cation-protein interactions. (C) 2000 Elsevier Scienc e B.V. All rights reserved.