title: Ketimine reductase/CRYM catalyzes reductive alkylamination of α-keto acids, confirming its function as an imine reductase.
abstract: Recently, crystalized mouse ketimine reductase/CRYM complexed with NADPH was found to have pyruvate bound in its active site. We demonstrate that the enzyme binds α-keto acids, such as pyruvate, in solution, and catalyzes the formation of N-alkyl-amino acids from alkylamines and α-keto acids (via reduction of imine intermediates), but at concentrations of these compounds not expected to be encountered in vivo. These findings confirm that, mechanistically, ketimine reductase/CRYM acts as a classical imine reductase and may explain the finding of bound pyruvate in the crystallized protein.
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, Balaclava Road, North Ryde, NSW, 2109, Australia. andre.hallen@students.mq.edu.au.
authors.forename: André
authors.initials: A
authors.lastname: Hallen
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, 10595, USA.
authors.forename: Arthur J L
authors.initials: AJ
authors.lastname: Cooper
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, Balaclava Road, North Ryde, NSW, 2109, Australia.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Smith
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, Balaclava Road, North Ryde, NSW, 2109, Australia.
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Jamie
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, Balaclava Road, North Ryde, NSW, 2109, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Karuso
mesh_terms: D000818:Animals; D002384:Catalysis; D003459:Crystallins / Q000737:chemistry*; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes / Q000737:chemistry*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000737:chemistry*; D010667:Phenylpyruvic Acids / Q000737:chemistry*; D000090803:mu-Crystallins
chemical_list: C000716469:CRYM protein, human; C000716470:Crym protein, mouse; D003459:Crystallins; D046912:Multiprotein Complexes; D010667:Phenylpyruvic Acids; D000587:Oxidoreductases Acting on CH-NH Group Donors; C056073:ketimine reductase; D000090803:mu-Crystallins; C031606:phenylpyruvic acid
keywords: Alkylamination; CRYM; Ketimine reductase; N-methyl amino acids