Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane
Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane
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DOI：
10.1016/s0014-5793(04)00209-1
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发表时间：
2004-04-30
期刊：
影响因子：
3.5
通讯作者：
Mattevi, A
中科院分区：
文献类型：
--
作者：
Binda, C;Hubálek, F;Mattevi, A
单胺氧化酶B（MAO B）是一种氧化芳烷基胺神经递质的线粒体外膜蛋白，是许多神经系统疾病的有价值的药物靶点。人MAO B的1.7埃分辨率结构显示该酶是二聚体，C-末端跨膜螺旋从每个单体突出并将蛋白质锚定到膜上。这种螺旋以与其他单端膜蛋白不同的方式从结构的底部垂直离开。暴露在蛋白质表面上的几个非极性环位于C-末端螺旋附近，提供额外的膜结合相互作用。这些环之一（残基99-112）也在打开和关闭MAO B活性位点空腔中起作用，这表明膜可能在控制底物结合中起作用。(C)2004年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Monoamine oxidase B (MAO B) is an outer mitochondrial membrane protein that oxidizes arylalkylamine neuro-transmitters 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. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.