Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane |
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Authors: | Binda Claudia Hubálek Frantisek Li Min Edmondson Dale E Mattevi Andrea |
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Affiliation: | Department of Genetics and Microbiology, University of Pavia, via Abbiategrasso 207, 27100 Pavia, Italy. |
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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. |
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Keywords: | Human monoamine oxidase B structure Mitochondrial membrane Monotopic Flavin |
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