催化天然环脱水的Azomycin生物合成酶RohQ的结构和机理。

IF 14.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Journal of the American Chemical Society Pub Date : 2025-07-11 DOI:10.1021/jacs.5c04341

Zi-Wang Wei, Phillip Daniel-Ivad, Li Zhang, Katherine S Ryan

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引用次数: 0

摘要

来自azomycin生物合成途径的RohQ催化自发环脱水生成2-氨基咪唑。在这里，我们报道了RohQ的结构和机制，并使用偶然结合的咪唑来确定活性位点残基。我们提出，催化作用发生在二聚体界面，使用两个关键的天冬氨酸残基进行质子转移步骤，以加速胍基和醛的3 × 104倍分子内环化，释放水。我们的工作扩展了我们对新出现的酶的理解，并提供了一个尚未探索的蛋白质家族的第一个结构和机制视图。

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Structure and Mechanism of the Azomycin Biosynthetic Enzyme RohQ That Catalyzes a Spontaneous Cyclodehydration.

RohQ from the azomycin biosynthetic pathway catalyzes a spontaneous cyclodehydration to form 2-aminoimidazole. Here we report the structure and mechanism of RohQ and use a serendipitously bound imidazole to pinpoint active site residues. We propose that catalysis occurs at the dimeric interface using two key aspartic acid residues for proton transfer steps to accelerate 3 × 10⁴-fold intramolecular cyclization of a guanidino group and aldehyde, releasing water. Our work expands our understanding of de novo emerged enzymes and provides the first structural and mechanistic view of a yet-unexplored protein family.

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来源期刊

Journal of the American Chemical Society 化学-化学综合

CiteScore

24.40

自引率

6.00%

发文量

2398

审稿时长

1.6 months

期刊介绍： The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.