The FAD binding sites of human monoamine oxidases A and B
The FAD binding sites of human monoamine oxidases A and B
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DOI：
10.1016/s0161-813x(03)00114-1
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发表时间：
2004-01-01
期刊：
影响因子：
3.4
通讯作者：
Mattevi, A
中科院分区：
文献类型：
--
作者：
Edmondson, DE;Binda, C;Mattevi, A
根据单胺氧化酶B(MAO B)的晶体结构，描述了共价的8α-S半胱氨酸-FAD与单胺氧化酶B(MAO B)中蛋白质部分相互作用的结构细节。二核苷酸以扩展的构象与蛋白质结合，与蛋白质的大部分键被鉴定为与氨基酸侧链、酰胺键和水分子的氢键。由于与FAD相互作用的氨基酸在单胺氧化酶A(MAO A)中是保守的，因此推测MAO A中的FAD结合部位与MAO B中的FAD结合部位非常相似。氧化还原活性的异烟肼环被埋在蛋白质中，而不是直接接触本体溶剂。观察到阴离子焦磷酸部分与Arg42之间存在静电相互作用。通常平坦的氧化黄素环在MAO B结合部位呈弯曲、褶皱的构象，这被认为有助于其催化活性。此结构信息随后用于解释先前关于将黄素类似物纳入MAO B或MAO A的研究。(C)2003 Elsevier Inc.保留所有权利。
The structural details of the interactions of the covalent 8alpha-S-cysteinyl-FAD with the protein moiety in monoamine oxidase B (MAO B) based on the MAO B crystal structure are described. The dinucleotide is bound to the protein in an extended conformation with the majority of the bonds to the protein identified as hydrogen bonds with amino acid side chains, amide bonds, and water molecules. Since those amino acids interacting with the FAD are conserved in monoamine oxidase A (MAO A), it is proposed that the FAD binding site in MAO A is quite similar to that in MAO B. The redox-active isoalloxazine ring is buried in the protein without direct access to bulk solvent. An electrostatic interaction is observed between the anionic pyrophosphate moiety and Arg42. The normally flat oxidized flavin ring is in a bent, puckered conformation in the MAO B binding site which is suggested to contribute to its reactivity in catalysis. This structural information is then used to explain previous studies on flavin analog incorporation into either MAO B or into MAO A. (C) 2003 Elsevier Inc. All rights reserved.