Crystal structure of dicamba monooxygenase: a Rieske nonheme oxygenase that catalyzes oxidative demethylation.

Crystal structure of dicamba monooxygenase: a Rieske nonheme oxygenase that catalyzes oxidative demethylation.
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DOI:
10.1016/j.jmb.2009.07.021
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发表时间:
2009-09-18
影响因子:
5.6
通讯作者:
Wilson, Mark A.
Wilson, Mark A.
中科院分区:
生物学2区
文献类型:
--
作者:
Dumitru, Razvan;Jiang, Wen Zhi;Weeks, Donald P.;Wilson, Mark A.

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麦草畏(3,6-二氯-2-甲氧基苯甲酸)是一种广泛使用的除草剂,可被土壤微生物有效降解。这些微生物使用一种新的Rieske非血红素加氧酶,麦草畏单加氧酶(DMO),催化麦草畏氧化脱甲基为3,6-二氯水杨酸(DCSA)和甲醛。我们已经确定了DMO在自由状态下的晶体结构,结合到其底物麦草畏,并结合到产品DCSA在2.10−1.75 Ω分辨率。的结构表明,DMO活性位点使用广泛的氢键和空间相互作用的组合,正确定向氯化,邻位取代的苯甲酸类底物的催化。与其他Rieske芳香族加氧酶不同,DMO氧化其底物的环外甲基,而不是芳香环。Rieske脱甲基酶的第一个晶体结构表明,Rieske加氧酶结构支架可以被增选以在异生物质底物上进行各种类型的反应。
Dicamba (3,6-dichloro-2-methoxybenzoic acid) is a widely used herbicide that is efficiently degraded by soil microbes. These microbes use a novel Rieske non-heme oxygenase, dicamba monooxygenase (DMO), to catalyze the oxidative demethylation of dicamba to 3,6-dichlorosalicylic acid (DCSA) and formaldehyde. We have determined the crystal structures of DMO in the free state, bound to its substrate dicamba, and bound to the product DCSA at 2.10−1.75 Å resolution. The structures show that the DMO active site uses a combination of extensive hydrogen bonding and steric interactions to correctly orient chlorinated, ortho-substituted benzoic acid-like substrates for catalysis. Unlike other Rieske aromatic oxygenases, DMO oxygenates the exocyclic methyl group, rather than the aromatic ring, of its substrate. This first crystal structure of a Rieske demethylase shows that the Rieske oxygenase structural scaffold can be co-opted to perform varied types of reactions on xenobiotic substrates.
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