tryptophan-tryptophylquinone and cyclopropylamine

Cyclopropylamine is a mechanism-based inhibitor of the quinoprotein methylamine dehydrogenase (MADH) from Paracoccus denitrificans. The resulting inactivation is accompanied by the formation of a covalent cross-link between the alpha and beta subunits of MADH. The results of site-directed mutagenesis studies indicate that Phe55 on the alpha subunit is required for this process. No cross-linking is seen with alphaF55A or alphaF55I MADH mutants. In contrast, with alphaF55E MADH cross-linking of subunits is observed. These results suggest a novel mechanistic role for a phenylalanine residue and the possible importance of protein dynamics in this enzyme mechanism.

Topics: Cross-Linking Reagents; Cyclopropanes; Indolequinones; Oxidoreductases Acting on CH-NH Group Donors; Paracoccus denitrificans; Phenylalanine; Point Mutation; Protein Subunits; Quinones; Tryptophan