Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane

FEBS Letters - Tập 564 - Trang 225-228 - 2004
Claudia Binda1, Frantisek Hubálek2, Min Li2, Dale E. Edmondson2, Andrea Mattevi1
1Department of Genetics and Microbiology, University of Pavia, Via Abbiategrasso 207, 27100 Pavia, Italy
2Departments of Biochemistry and Chemistry, Emory University, Clifton Road 1510, Atlanta, GA 30322, USA

Tóm tắt

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 Å 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.

Tài liệu tham khảo

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FEBS Letters

Tập 564

225-228

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