title: Inter-subunit cross-linking of methylamine dehydrogenase by cyclopropylamine requires residue alphaPhe55.
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.
authors.affiliation: Department of Biochemistry, The University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Sun
authors.forename: Victor L
authors.initials: VL
authors.lastname: Davidson
mesh_terms: D003432:Cross-Linking Reagents / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology*; D045563:Indolequinones; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010231:Paracoccus denitrificans / Q000201:enzymology; D010649:Phenylalanine / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D021122:Protein Subunits; D011809:Quinones / Q000378:metabolism*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D003521:Cyclopropanes; D045563:Indolequinones; D021122:Protein Subunits; D011809:Quinones; C070569:tryptophan tryptophylquinone; D010649:Phenylalanine; D014364:Tryptophan; C067351:cyclopropylamine; C021567:methylamine dehydrogenase; D000587:Oxidoreductases Acting on CH-NH Group Donors