2VZ2

Human MAO B in complex with mofegiline

Summary for 2VZ2

• Entry DOI: 10.2210/pdb2vz2/pdb
• Related: 1GOS 1H8R 1OJ9 1OJA 1OJB 1OJC 1OJD 1S2Q 1S2Y 1S3B 1S3E 2BK3 2BK4 2BK5 2BYB 2C64 2C65 2C66 2C67 2C70 2C72 2C73 2C75 2C76 2V5Z 2V60 2V61 2VRL 2VRM
• Descriptor: AMINE OXIDASE [FLAVIN-CONTAINING] B, FLAVIN-ADENINE DINUCLEOTIDE, (1Z)-4-(4-FLUOROPHENYL)-2-METHYLIDENEBUTAN-1-IMINE, ... (5 entities in total)
• Functional Keywords: oxidoreductase, inhibitor binding, flavoprotein, mitochondrion, transmembrane, human monoamine oxidase, mitochondrion outer membrane, fad, flavin, membrane, mofegiline, acetylation
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Mitochondrion outer membrane; Single-pass type IV membrane protein; Cytoplasmic side: P27338
• Total number of polymer chains: 2
• Total formula weight: 120274.10

Authors

Bonivento, D.,Mattevi, A. (deposition date: 2008-07-29, release date: 2008-12-16, Last modification date: 2023-12-13)

Primary citation

Milczek, E.M.,Bonivento, D.,Binda, C.,Mattevi, A.,McDonald, I.A.,Edmondson, D.E.
Structural and mechanistic studies of mofegiline inhibition of recombinant human monoamine oxidase B.
J. Med. Chem., 51:8019-8026, 2008

PubMed Abstract: 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 K(i) 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 (lambda(max) approximately 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.

PubMed: 19053775
DOI: 10.1021/jm8011867

Experimental method

X-RAY DIFFRACTION (2.3 Å)