Copper binding by a unique family of metalloproteins is dependent on kynurenine formation

Copper binding by a unique family of metalloproteins is dependent on kynurenine formation
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独特的金属蛋白家族与铜的结合取决于犬尿氨酸的形成

DOI:
10.1073/pnas.2100680118
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发表时间:
2021
期刊:
Proceedings of the National Academy of Sciences
影响因子:
--
通讯作者:
Rosenzweig, Amy C.
Rosenzweig, Amy C.
中科院分区:
--
文献类型:
--
作者:
Manesis, Anastasia C.;Jodts, Richard J.;Hoffman, Brian M.;Rosenzweig, Amy C.

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一些甲烷氧化细菌使用核糖体合成的、后修饰的天然产物甲烷氧化菌素(Mbn)来获得铜用于其主要代谢酶,颗粒甲烷单加氧酶。编码生物合成和转运Mbns的机制的操纵子通常包括两种蛋白质MbnH和MbnB的基因,这两种蛋白质在与铜稳态相关的其他基因组背景中也被发现为一对。虽然MbnH蛋白是细菌二血红素细胞色素过氧化物酶(bCcP)/MauG超家族的成员,但MbnH的结构和功能、两种蛋白之间的关系及其在铜稳态中的作用仍不清楚。来自甲烷营养型发孢甲基弯菌OB 3b的MbR的生物化学表征现在揭示,MbR以高亲和力结合以+1氧化态存在的单个铜离子。铜在体内与MbnH的结合依赖于保守的WxW基序中的第一个色氨酸氧化为犬尿氨酸,这是通过MbnH与MbnH的相互作用发生的转化。2.04 μ m-分辨率的MbdR晶体结构揭示了一个独特的折叠和一个不寻常的铜结合位点,涉及组氨酸,甲硫氨酸,溶剂配体和犬尿氨酸。尽管犬尿氨酸残基可能不充当Cu I初级球配体,但其位于距离Cu I离子约2.9 nm处,其存在是铜结合所需的。基因组邻域分析表明,Mbatomic蛋白,并通过扩展犬尿氨酸含铜位点,是广泛的,并可能发挥不同的作用,在微生物铜稳态。
Some methane-oxidizing bacteria use the ribosomally synthesized, posttranslationally modified natural product methanobactin (Mbn) to acquire copper for their primary metabolic enzyme, particulate methane monooxygenase. The operons encoding the machinery to biosynthesize and transport Mbns typically include genes for two proteins, MbnH and MbnP, which are also found as a pair in other genomic contexts related to copper homeostasis. While the MbnH protein, a member of the bacterial diheme cytochromecperoxidase (bCcP)/MauG superfamily, has been characterized, the structure and function of MbnP, the relationship between the two proteins, and their role in copper homeostasis remain unclear. Biochemical characterization of MbnP from the methanotrophMethylosinus trichosporiumOB3b now reveals that MbnP binds a single copper ion, present in the +1 oxidation state, with high affinity. Copper binding to MbnP in vivo is dependent on oxidation of the first tryptophan in a conserved WxW motif to a kynurenine, a transformation that occurs through an interaction of MbnH with MbnP. The 2.04-Å-resolution crystal structure of MbnP reveals a unique fold and an unusual copper-binding site involving a histidine, a methionine, a solvent ligand, and the kynurenine. Although the kynurenine residue may not serve as a CuIprimary-sphere ligand, being positioned ∼2.9 Å away from the CuIion, its presence is required for copper binding. Genomic neighborhood analysis indicates that MbnP proteins, and by extension kynurenine-containing copper sites, are widespread and may play diverse roles in microbial copper homeostasis.
DOI: 10.1039/c5mt00289c
发表时间: 2016-09-01
期刊: Metallomics : integrated biometal science
影响因子: --
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DOI: 10.1107/s0108270100004984
发表时间: 2000
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