title: Medical implications from the crystal structure of a copper-containing amine oxidase complexed with the antidepressant drug tranylcypromine.
abstract: The X-ray crystal structure of the copper-containing quinoprotein amine oxidase from E. coli has been determined in complex with the antidepressant drug tranylcypromine to 2.4 A resolution. The drug is a racemic mix of two enantiomers, but only one is seen bound to the enzyme. The other enantiomer is not acting as a substrate for the enzyme as no catalytic activity was detected when the enzyme was initially exposed to the drug. The inhibition of human copper amine oxidases could be a source of side-effects in its use as an antidepressant to inhibit the flavin-containing monoamine oxidases in the brain.
authors.affiliation: Astbury Centre for Structural Molecular Biology, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. wilmo004@umn.edu
authors.forename: Carrie M
authors.initials: CM
authors.lastname: Wilmot
authors.forename: Colin G
authors.initials: CG
authors.lastname: Saysell
authors.forename: Aidan
authors.initials: A
authors.lastname: Blessington
authors.forename: Danyl A
authors.initials: DA
authors.lastname: Conn
authors.forename: Christian R
authors.initials: CR
authors.lastname: Kurtis
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McPherson
authors.forename: Peter F
authors.initials: PF
authors.lastname: Knowles
authors.forename: Simon E V
authors.initials: SE
authors.lastname: Phillips
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000737:chemistry* / Q000378:metabolism; D000928:Antidepressive Agents / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray / Q000379:methods; D004926:Escherichia coli / Q000201:enzymology; D008958:Models, Molecular; D014191:Tranylcypromine / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D014191:Tranylcypromine; D006631:Amine Oxidase (Copper-Containing)