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首页> 外文期刊>Journal of Molecular Biology >Structure of rat monoamine oxidase a and its specific recognitions for substrates and inhibitors.
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Structure of rat monoamine oxidase a and its specific recognitions for substrates and inhibitors.

机译：大鼠单胺氧化酶a的结构及其对底物和抑制剂的特异性识别。

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摘要

Monoamine oxidase (MAO), a mitochondrial outer membrane enzyme, catalyzes the degradation of neurotransmitters in the central nervous system and is the target for anti-depression drug design. Two subtypes of MAO, MAOA and MAOB, are similar in primary sequences but have unique substrate and inhibitor specificities. The structures of human MAOB complexed with various inhibitors were reported early. To understand the mechanisms of specific substrate and inhibitor recognitions of MAOA and MAOB, we have determined the crystal structure of rat MAOA complexed with the specific inhibitor, clorgyline, at 3.2A resolution. The comparison of the structures between MAOA and MAOB clearly explains the specificity of clorgyline for MAOA inhibition. The fitting of serotonin into the binding pockets of MAOs demonstrates that MAOB Tyr326 would block access of the 5-hydroxy group of serotonin into the enzyme. These results will lead to further understanding of the MAOA function and to new anti-depression drug design. Thisstudy also presents that MAOA has a transmembrane helix at the C-terminal region. This is the first crystal structure of membrane protein with an isolated transmembrane helix.
机译：单胺氧化酶（MAO）是一种线粒体外膜酶，可催化中枢神经系统中神经递质的降解，是抗抑郁药设计的目标。 MAO的两个亚型，MAOA和MAOB，在一级序列中相似，但具有独特的底物和抑制剂特异性。早期报道了与各种抑制剂复合的人MAOB的结构。为了了解MAOA和MAOB的特异性底物和抑制剂识别的机制，我们确定了与MAA和特异性抑制剂克洛可林复合的大鼠MAOA的晶体结构，分辨率为3.2A。 MAOA和MAOB之间结构的比较清楚地说明了氯吉兰对MAOA抑制的特异性。将5-羟色胺装入MAO的结合口袋中表明，MAOB Tyr326将阻止5-羟色胺的5-羟基进入酶。这些结果将导致对MAOA功能的进一步了解和新的抗抑郁药设计。该研究还表明，MAOA在C端区域具有跨膜螺旋。这是具有分离的跨膜螺旋的膜蛋白的第一个晶体结构。

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