色氨酸裂解酶（NosL）的机理研究：鉴定氰化物为反应产物。
Mechanistic Studies on Tryptophan Lyase (NosL): Identification of Cyanide as a Reaction Product.
机构信息
Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
出版信息
J Am Chem Soc. 2018 Jan 17;140(2):542-545. doi: 10.1021/jacs.7b09000. Epub 2018 Jan 2.
Abstract
Tryptophan lyase (NosL) catalyzes the formation of 3-methylindole-2-carboxylic acid and 3-methylindole from l-tryptophan. In this paper, we provide evidence supporting a formate radical intermediate and demonstrate that cyanide is a byproduct of the NosL-catalyzed reaction with l-tryptophan. These experiments require a major revision of the NosL mechanism and uncover an unanticipated connection between NosL and HydG, the radical SAM enzyme that forms cyanide and carbon monoxide from tyrosine during the biosynthesis of the metallo-cluster of the [Fe-Fe] hydrogenase.
摘要
色氨酸裂解酶（NosL）催化 l-色氨酸生成 3-甲基吲哚-2-羧酸和 3-甲基吲哚。本文提供了支持甲酸盐自由基中间体形成的证据，并表明氰化物是 NosL 催化 l-色氨酸反应的副产物。这些实验需要对 NosL 机制进行重大修订，并揭示了 NosL 与 HydG 之间的意外联系，HydG 是一种自由基 SAM 酶，在 [Fe-Fe]氢化酶金属簇的生物合成过程中，将酪氨酸转化为氰化物和一氧化碳。
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J Am Chem Soc. 2017 Aug 16;139(32):10952-10955. doi: 10.1021/jacs.7b04209. Epub 2017 Aug 3.
2
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3
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6
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Science. 2016 Mar 18;351(6279):1320-3. doi: 10.1126/science.aad8995.
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