Isolation and Sequencing of Salsolinol Synthase, an Enzyme Catalyzing Salsolinol Biosynthesis,ACS Chemical Neuroscience

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Isolation and Sequencing of Salsolinol Synthase, an Enzyme Catalyzing Salsolinol Biosynthesis
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2018-03-30 00:00:00 , DOI: 10.1021/acschemneuro.8b00023
Xuechai Chen ₁ , Xiaotong Zheng ₁ , Sakhawat Ali ₂ , Minjun Guo ₂ , Rugang Zhong ₁ , Zixuan Chen ₃ , Yongqian Zhang ₃ , Hong Qing ₃ , Yulin Deng ₃

Affiliation

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline), a derivate of dopamine, is suspected to be the most probable neurotoxin in the degeneration of dopaminergic neurons. Numerous hypotheses regarding its pathophysiological roles have been raised, especially related to Parkinson’s disease and alcohol addiction. In the mammalian brain, salsolinol may be enzymatically synthesized by salsolinol synthase from dopamine and acetaldehyde. However, the direct evidence of its biosynthesis was still missing. In this study, we purified salsolinol synthase from rat brain by a systematical procedure involving acid precipitation, ultrafiltration, and hydrophilic interaction chromatography. The molecular weight of salsolinol synthase determined by MALDI-TOF MS is 8622.29 Da, comprising 77 amino acids (MQIFVKTLTG KTITLEVEPS DTIKNVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKKSTLHLV LRLRVDY). Homology analysis showed that the enzyme is a ubiquitin-like protein, with a difference of four amino acids, which suggests it is a novel protein. After it was overexpressed in eukaryotic cells, the production of salsolinol was significantly increased as compared with control, confirming the catalytic function of this enzyme. To our knowledge, it is the first systematic purification and sequencing of salsolinol synthase. Together, this work reveals a formerly anonymous protein and urges further exploration of its possible prognostic value and implications in Parkinson’s disease and other related disorders.

中文翻译：

催化Salsolinol生物合成的酶Salsolinol合酶的分离和测序

多巴胺的衍生物Salsolinol（1-甲基-6,7-二羟基-1,2,3,4-四氢异喹啉）被怀疑是多巴胺能神经元变性中最可能的神经毒素。关于其病理生理作用的许多假设已经提出，特别是与帕金森氏病和酒精成瘾有关。在哺乳动物的脑中，Salsolinol合成酶可以由多巴胺和乙醛酶法合成Salsolinol。但是，其生物合成的直接证据仍然缺失。在这项研究中，我们通过涉及酸沉淀，超滤和亲水相互作用色谱的系统程序从鼠脑中纯化了Salsolinol合酶。MALDI-TOF MS测定的Salsolinol合酶的分子量为8622.29 Da，包含77个氨基酸（MQIFVKTLTG KTITLEVEPS DTIKNVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKKSTLHLV LRLRVDY）。同源性分析表明该酶是一种泛素样蛋白，具有四个氨基酸的差异，这表明它是一种新型蛋白。在真核细胞中过表达后，与对照相比，沙丁胺醇的产量显着增加，证实了该酶的催化功能。据我们所知，这是Salsolinol合酶的第一个系统纯化和测序。总之，这项工作揭示了一种以前匿名的蛋白质，并敦促进一步探索其可能的预后价值及其对帕金森氏病和其他相关疾病的影响。具有四个氨基酸的差异，这表明它是一种新型蛋白质。在真核细胞中过表达后，与对照相比，沙丁胺醇的产量显着增加，证实了该酶的催化功能。据我们所知，这是Salsolinol合酶的第一个系统纯化和测序。总之，这项工作揭示了一种以前匿名的蛋白质，并敦促进一步探索其可能的预后价值及其对帕金森氏病和其他相关疾病的影响。具有四个氨基酸的差异，这表明它是一种新型蛋白质。在真核细胞中过表达后，与对照相比，沙丁胺醇的产量显着增加，证实了该酶的催化功能。据我们所知，这是Salsolinol合酶的第一个系统纯化和测序。总之，这项工作揭示了一种以前匿名的蛋白质，并敦促进一步探索其可能的预后价值及其对帕金森氏病和其他相关疾病的影响。这是Salsolinol合酶的第一个系统纯化和测序。总之，这项工作揭示了一种以前匿名的蛋白质，并敦促进一步探索其可能的预后价值及其对帕金森氏病和其他相关疾病的影响。这是Salsolinol合酶的第一个系统纯化和测序。总之，这项工作揭示了一种以前匿名的蛋白质，并敦促进一步探索其可能的预后价值及其对帕金森氏病和其他相关疾病的影响。

更新日期：2018-03-30

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