Medical implications from the crystal structure of a copper-containing amine oxidase complexed with the antidepressant drug tranylcypromine.
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.
Wilmot
Carrie M
CM
Astbury Centre for Structural Molecular Biology, School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. wilmo004@umn.edu
Saysell
Colin G
CG
Blessington
Aidan
A
Conn
Danyl A
DA
Kurtis
Christian R
CR
McPherson
Michael J
MJ
Knowles
Peter F
PF
Phillips
Simon E V
SE
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
D000928:Antidepressive Agents; D014191:Tranylcypromine; D006631:Amine Oxidase (Copper-Containing)