title: Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane.
abstract: Monoamine oxidase B (MAO B) is an outer mitochondrial membrane protein that oxidizes arylalkylamine neurotransmitters and has been a valuable drug target for many neurological disorders. The 1.7 angstrom resolution structure of human MAO B shows the enzyme is dimeric with a C-terminal transmembrane helix protruding from each monomer and anchoring the protein to the membrane. This helix departs perpendicularly from the base of the structure in a different way with respect to other monotopic membrane proteins. Several apolar loops exposed on the protein surface are located in proximity of the C-terminal helix, providing additional membrane-binding interactions. One of these loops (residues 99-112) also functions in opening and closing the MAO B active site cavity, which suggests that the membrane may have a role in controlling substrate binding.
authors.affiliation: Department of Genetics and Microbiology, University of Pavia, via Abbiategrasso 207, 27100 Pavia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Binda
authors.forename: Frantisek
authors.initials: F
authors.lastname: Hubálek
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Dale E
authors.initials: DE
authors.lastname: Edmondson
authors.forename: Andrea
authors.initials: A
authors.lastname: Mattevi
mesh_terms: D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy; D017434:Protein Structure, Tertiary
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D008995:Monoamine Oxidase