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Engineering a C-terminally modified human flavin containing monooxygenase

机译:工程含有单氧基酶的C末端改性人黄素

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Human flavin containing monooxygenase 3 is a drug-metabolizing enzyme involved in the oxidation of many drugs, chemicals and xenobiotics. It is predominantly expressed in the liver where its substrates, generally soft nucleophiles are transformed into more polar metabolites. The enzyme is attached to the smooth endoplasmic reti-culum membrane, where its reduced flavin group binds molecular oxygen and readily performs nucleophilic attack on the substrates. To date the structure of hFMO3 has not been solved due to difficulties in the crystallization of microsomal, membrane-bound proteins. In the present study a molecular model of hFMO3 is constructed, exploited by in silico molecular dynamics experiments to identify the membrane anchor and used for the rational design of a soluble truncated hFMO3 enzyme.
机译:含有单氧化酶3的人黄素是涉及许多药物,化学品和异种菌药的氧化的药物代谢酶。它主要在肝脏中表达,其中其基材,通常软的亲核试剂转化为更偏极的代谢物。酶附着在光滑的内质复制膜上,其减少的黄素基团结合分子氧,并且容易对基板进行亲核攻击。迄今为止,由于微粒体,膜结合蛋白质的结晶困难,HFMO3的结构尚未解决。在本研究中,通过在硅分子动力学实验中实施HFMO3的分子模型,以鉴定膜锚并用于可溶性截短的HFMO3酶的合理设计。

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