Molecular and mechanistic properties of the membrane-bound mitochondrial monoamine oxidases.
Molecular and mechanistic properties of the membrane-bound mitochondrial monoamine oxidases.
复制标题
DOI：
10.1021/bi900413g
复制
发表时间：
2009-05-26
期刊：
影响因子：
2.9
通讯作者：
Mattevi, Andrea
中科院分区：
文献类型：
--
作者：
Edmondson, Dale E.;Binda, Claudia;Wang, Jin;Upadhyay, Anup K.;Mattevi, Andrea
过去十年中，我们对MAO A和MAO B的结构和机制的认识取得了重大进展，这两种物质是特异性抑制剂的药理学靶点。在这两种酶中，晶体学和生物化学数据显示它们各自的C-末端跨膜螺旋将酶锚在线粒体外膜上。脉冲EPR数据显示，这两种酶是二聚体在其膜结合的形式与协议之间的距离测量其结晶形式。活性位点定向自旋标记膜制剂之间的距离测量显示出良好的协议与晶体学数据估计。我们对开发特异性可逆MAO B抑制剂的要求的了解处于相当成熟的状态。关于高度特异性可逆的MAO A抑制剂的结构要求知之甚少。尽管它们的70%序列同一性和Cα-折叠的相似性，但这两种酶表现出显著的功能和结构差异，可用于开发高度特异性抑制剂的最终目标。这篇综述总结了目前的结构和机制的信息，可用于发展未来的高度特异性的神经保护剂和心脏保护剂。
The last decade has brought major advances in our knowledge of the structures and mechanisms of MAO A and MAO B, which are pharmacological targets for specific inhibitors. In both enzymes, crystallographic and biochemical data show their respective C-terminal transmembrane helices anchor the enzymes to the outer mitochondrial membrane. Pulsed EPR data show both enzymes are dimeric in their membrane-bound forms with agreement between distances measured in their crystalline forms. Distances measure between active-site directed spin labels in membrane preparations show excellent agreement with those estimated from crystallographic data. Our knowledge of requirements for development of specific reversible MAO B inhibitors is in a fairly mature status. Less is known regarding the structural requirements for highly specific reversible MAO A inhibitors. In spite of their 70% sequence identity and similarities of Cα-folds, the two enzymes exhibit significant functional and structural differences that can be exploited in the ultimate goal of the development of highly specific inhibitors. This review summarizes the current structural and mechanistic information available that can be utilized in the development of future highly specific neuroprotectants and cardioprotectants.
登录
查看更多内容
DOI：
10.1046/j.1432-1033.2001.02462.x
发表时间：
2001-11-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Harris, CM;Pollegioni, L;Ghisla, S
通讯作者：
Ghisla, S
影响因子：
4.1
作者：
Chen, Jack J.;Swope, David M.
通讯作者：
Swope, David M.
影响因子：
2.9
作者：
EDMONDSON, DE;BHATTACHARYYA, AK;WALKER, MC
通讯作者：
WALKER, MC
影响因子：
7.3
作者：
Gentili, Francesco;Pizzinat, Nathalie;Giannella, Mario
通讯作者：
Giannella, Mario
影响因子：
5.3
作者：
Andrés, AM;Soldevila, M;Bertranpetit, J
通讯作者：
Bertranpetit, J