1GOS

Human Monoamine Oxidase B

Summary for 1GOS

• Entry DOI: 10.2210/pdb1gos/pdb
• Related: 1H8R
• Descriptor: MONOAMINE OXIDASE, FLAVIN-ADENINE DINUCLEOTIDE, N-[(E)-METHYL](PHENYL)-N-[(E)-2-PROPENYLIDENE]METHANAMINIUM (3 entities in total)
• Functional Keywords: oxidoreductase, fad-containing amine oxidase
• 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: 119575.09

Authors

Binda, C.,Newton-Vinson, P.,Hubalek, F.,Edmondson, D.E.,Mattevi, A. (deposition date: 2001-10-26, release date: 2001-11-29, Last modification date: 2024-11-13)

Primary citation

Binda, C.,Newton-Vinson, P.,Hubalek, F.,Edmondson, D.E.,Mattevi, A.
Structure of Human Monoamine Oxidase B, a Drug Target for the Treatment of Neurological Disorders
Nat.Struct.Biol., 9:22-, 2001

PubMed Abstract: Monoamine oxidase B (MAO B) is a mitochondrial outermembrane flavoenzyme that is a well-known target for antidepressant and neuroprotective drugs. We determined the structure of the human enzyme to 3 A resolution. The enzyme binds to the membrane through a C-terminal transmembrane helix and apolar loops located at various positions in the sequence. The electron density shows that pargyline, an analog of the clinically used MAO B inhibitor, deprenyl, binds covalently to the flavin N5 atom. The active site of MAO B consists of a 420 A(3)-hydrophobic substrate cavity interconnected to an entrance cavity of 290 A(3). The recognition site for the substrate amino group is an aromatic cage formed by Tyr 398 and Tyr 435. The structure provides a framework for probing the catalytic mechanism, understanding the differences between the B- and A-monoamine oxidase isoforms and designing specific inhibitors.

PubMed: 11753429
DOI: 10.1038/NSB732

Experimental method

X-RAY DIFFRACTION (3 Å)