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Author Notes:

To whom correspondence should be addressed: (D.E.E.) Tel. 404-727-5972. Fax: 404-727-2738. Email: deedmon@emory.edu

Research Funding:

National Institute of General Medical Sciences : NIGMS

National Institute of Neurological Disorders and Stroke : NINDS


  • Monoamine Oxidase
  • Mofegiline
  • MAO-B
  • MAO-B Inhibitor
  • Covalent Flavin Adduct

Structural and Mechanistic Studies of Mofegiline Inhibition of Recombinant Human Monoamine Oxidase B


Journal Title:

Journal of Medicinal Chemistry


Volume 51, Number 24


, Pages 8019-8026

Type of Work:

Article | Post-print: After Peer Review


Mechanistic and structural studies have been carried out to investigate the molecular basis for the irreversible inhibition of human MAO-B by mofegiline. Competitive inhibition with substrate shows an apparent Ki of 28 nM. Irreversible inhibition of MAO-B occurs with a 1:1 molar stoichiometry with no observable catalytic turnover. The absorption spectral properties of mofegiline inhibited MAO-B show features (λmax ≃ 450 nm) unlike those of traditional flavin N(5) or C(4a) adducts. Visible and near UV circular dichroism spectra of the mofegiline-MAO-B adduct shows a negative peak at 340 nm with an intensity similar to that of N(5) flavocyanine adducts. The x-ray crystal structure of the mofegiline-MAO-B adduct shows a covalent bond between the flavin cofactor N(5) with the distal allylamine carbon atom as well as the absence of the fluorine atom. A mechanism to explain these structural and spectral data is proposed.

Copyright information:

© 2008 American Chemical Society

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