Premium
Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane
Author(s) -
Binda Claudia,
Hubálek Frantisek,
Li Min,
Edmondson Dale E.,
Mattevi Andrea
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(04)00209-1
Subject(s) - outer membrane efflux proteins , monoamine oxidase , helix (gastropod) , inner mitochondrial membrane , chemistry , membrane , biophysics , membrane protein , transmembrane protein , intermembrane space , enzyme , transmembrane domain , stereochemistry , active site , monoamine oxidase a , bacterial outer membrane , biochemistry , integral membrane protein , biology , receptor , ecology , escherichia coli , snail , gene
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.