Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA.
Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA.
Nat Chem Biol. 2021 Mar;17(3):344-350. doi: 10.1038/s41589-020-00712-3. Epub 2021 Jan 11.
Nicotine oxidoreductase (NicA2), a member of the flavin-containing amine oxidase family, is of medical relevance as it shows potential as a therapeutic to aid cessation of smoking due to its ability to oxidize nicotine into a non-psychoactive metabolite. However, the use of NicA2 in this capacity is stymied by its dismal O-dependent activity. Unlike other enzymes in the amine oxidase family, NicA2 reacts very slowly with O, severely limiting its nicotine-degrading activity. Instead of using O as an oxidant, we discovered that NicA2 donates electrons to a cytochrome c, which means that NicA2 is actually a dehydrogenase. This is surprising, as enzymes of the flavin-containing amine oxidase family were invariably thought to use O as an electron acceptor. Our findings establish new perspectives for engineering this potentially useful therapeutic and prompt a reconsideration of the term 'oxidase' in referring to members of the flavin-containing amine 'oxidase' family.
尼古丁氧化还原酶（NicA2）是黄素胺氧化酶家族的成员，由于其能够将尼古丁氧化成非致瘾代谢物，因此具有作为戒烟辅助治疗的潜力，具有医学相关性。然而，由于其 O 依赖性活性不佳，NicA2 的这种用途受到阻碍。与黄素胺氧化酶家族中的其他酶不同，NicA2 与 O 的反应非常缓慢，严重限制了其尼古丁降解活性。我们发现 NicA2 不是将 O 用作氧化剂，而是将电子捐赠给细胞色素 c，这意味着 NicA2 实际上是一种脱氢酶。这令人惊讶，因为黄素胺氧化酶家族的酶一直被认为使用 O 作为电子受体。我们的发现为工程改造这种潜在有用的治疗方法提供了新的视角，并促使人们重新考虑在提到黄素胺氧化酶家族成员时使用“氧化酶”一词。
