Medical implications from the crystal structure of a copper-containing amine oxidase complexed with the antidepressant drug tranylcypromine

Carrie M Wilmot, Colin G. Saysell, Aidan Blessington, Danyl A. Conn, Christian R. Kurtis, Michael J. McPherson, Peter F. Knowles, Simon E.V. Phillips

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19 Scopus citations

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 Å 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.

Original languageEnglish (US)
Pages (from-to)301-305
Number of pages5
JournalFEBS Letters
Volume576
Issue number3
DOIs
StatePublished - Oct 22 2004

Bibliographical note

Funding Information:
This work was supported by a Howard Hughes Medical Institute International Research Scholar award to SEVP, a grant from the UK Biotechnology and Biological Sciences Research Council (BBSRC) and the BBSRC Structural Biology Initiative. The authors thank Veronica Blakeley for preparing the protein, the staff at the Daresbury SRS, particularly Pierre Rizkallah, Brad Elmore for sequence alignments and Arwen Pearson for help with figures. The structure factors and model coordinates have been deposited with the Protein Data Bank, accession code 1LVN.

Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.

Keywords

  • Amine oxidase
  • Copper metalloprotein
  • Quinoprotein
  • Tranylcypromine
  • X-ray crystallography

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