Hydrazine and amphetamine binding to amine oxidases: Old drugs with new prospects

P. Knowles, C. Kurtis, J. Murray, C. Saysell, W. Tambyrajah, C. Wilmot, M. McPherson, S. Phillips, D. Dooley, D. Brown, M. Rogers, M. Mure

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Tranylcypromine (TCP), an amphetamine, is a reversible inhibitor of copper-containing amine oxidases. We have solved the structure of the complex of TCP with the amine oxidase from E. coli (ECAO) and shown that only the (+)-enantiomer of TCP binds. Kinetic studies on 2-phenylethylamine and TCP binding to wild-type ECAO and mutational variants fully support the model in which binding of the protonated amine is the first step in the catalytic cycle. Hydrazines are irreversible inhibitors of copper-containing amine oxidases. Binding of hydrazines leads to an adduct ("Adduct 1") with a chromophore at 430nm which converts at higher pH to another adduct ("Adduct 2") with a chromophore at 520nm. We have determined the structures of Adduct 1 and 2 for 2-hydrazinopyridine reacted with ECAO. It has been found that Adduct 1 corresponds to the hydrazone and azo tautomers whilst Adduct 2 corresponds to the azo tautomer coordinated to the active site copper. The implications of these results in developing more specific drugs are discussed.

Original languageEnglish (US)
Pages (from-to)743-746
Number of pages4
JournalJournal of Neural Transmission
Issue number6
StatePublished - Jun 1 2007


  • 2-hydrazinopyridine (2-HP)
  • 2-phenylcyclopropylamine (TCP)
  • Amine oxidase
  • Trihydroxyphenylalanine (TPQ)
  • pH


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