The activation of the metal-containing regulatory protein NiaR from Thermotoga maritima by its effector, nicotinic acid

IF 2.7 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Biological Inorganic Chemistry Pub Date : 2025-02-03 DOI:10.1007/s00775-025-02096-y

Wai Chung Dorothy Cheng, Yuxin Li, Maileen Nakashima, Pierre Moënne-Loccoz, Katherine W. Rush, Arthur Glasfeld

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Abstract

NiaR is a regulatory protein that represses the expression of proteins involved in the de novo biosynthesis and uptake of nicotinic acid (NA), with NA acting as a co-repressor. The previously published structure of NiaR from Thermotoga maritima (TmNiaR) identified it as a functional homodimer containing a transition metal ion in a suspected NA-binding pocket. Here, we present the crystal structure of NA bound to the iron-metalated form of TmNiaR. Supported by spectroscopic and solution studies, this structure shows that NA binds to a protein-bound ferrous ion via its ring nitrogen. In addition, the carboxylate group on NA interacts with Tyr108 from the dyad-related subunit, repositioning the likely DNA-binding domains of the dimer to promote high-affinity interactions with DNA operators. The specificity of TmNiaR for NA can be explained by the hydrogen bonding scheme within the NA-binding pocket.

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海洋热蝇含金属调控蛋白NiaR的激活及其效应物烟酸。

NiaR是一种调节蛋白，可抑制参与烟酸（NA）新生生物合成和摄取的蛋白的表达，NA可作为协同抑制因子。先前发表的来自Thermotoga maritima的NiaR结构（TmNiaR）鉴定出它是一种功能同源二聚体，在可疑的na结合口袋中含有过渡金属离子。在这里，我们展示了NA与铁金属化形式的TmNiaR结合的晶体结构。在光谱和溶液研究的支持下，该结构表明NA通过其环氮与蛋白质结合的铁离子结合。此外，NA上的羧酸基团与来自二聚体相关亚基的Tyr108相互作用，重新定位二聚体可能的DNA结合域，以促进与DNA操作子的高亲和力相互作用。TmNiaR对NA的特异性可以通过NA结合袋内的氢键方案来解释。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Biological Inorganic Chemistry 化学-生化与分子生物学

CiteScore

5.90

自引率

3.30%

发文量

审稿时长

3 months

期刊介绍： Biological inorganic chemistry is a growing field of science that embraces the principles of biology and inorganic chemistry and impacts other fields ranging from medicine to the environment. JBIC (Journal of Biological Inorganic Chemistry) seeks to promote this field internationally. The Journal is primarily concerned with advances in understanding the role of metal ions within a biological matrix—be it a protein, DNA/RNA, or a cell, as well as appropriate model studies. Manuscripts describing high-quality original research on the above topics in English are invited for submission to this Journal. The Journal publishes original articles, minireviews, and commentaries on debated issues.