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Updated: Sep 11, 2026

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Inter-subunit cross-linking of methylamine dehydrogenase by cyclopropylamine requires residue alphaPhe55
Dapeng Sun1, Victor L Davidson
1Department of Biochemistry, The University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Abstract:
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.
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