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Identification of a copper ion recognition peptide sequence in the subunit II of cytochrome c oxidase: a combined theoretical and experimental study
JBIC Journal of Biological Inorganic Chemistry ( IF 3 ) Pub Date : 2021-04-29 , DOI: 10.1007/s00775-021-01867-7
Dwaipayan Dutta Gupta 1 , Imon Mandal 1 , Chandrani Nayak 2 , Shambhu Nath Jha 2 , Dibyendu Bhattacharyya 2 , Ravindra Venkatramani 1 , Shyamalava Mazumdar 1
Affiliation  

The role of the pentapeptide, NHSFM, derived from the surface exposed part of the metal ion binding loop of the subunit II of cytochrome c oxidase on the maturation of the binuclear purple CuA center of the enzyme has been investigated using several experimental and computational methods. The copper ion was found to form 1:1 complex of the pentapeptide with a binding constant ~ 104 M−1 to 105 M−1, where a 4 ligand coordination from the peptide in a type 2 copper center was revealed. The pH dependence of the metal–peptide was associated with a \({\text{p}}K_{{\text{a}}}\) of ~ 10 suggesting deprotonation of the N-terminal amine. EXAFS studies as well as DFT calculations of the metal–peptide complexes revealed pH dependent changes in the metal–ligand bond distances. Spectroscopic properties of the metal peptides calculated from TDDFT studies agreed with the experimental results. Restrained molecular dynamics (RMD) simulations indicated coordination of a carbonyl oxygen from the asparagine (N) side chain and of water molecules apart from histidine (H), methionine (M) and terminal amine of asparagine (N) in a distorted square planar geometry of Cu–NHSFM. Analyses of the backbone distances as well as B-factors for the metal peptide suggested that the peptide backbone becomes more compact and rigid on binding of the metal ion. This indicated that binding of copper ion to this pentapeptide in the protein possibly cause movement of the protein backbone bringing other coordinating residues closer to the copper ion, and thus helping in sequential uptake of copper ions to the protein.

Graphic abstract



中文翻译:

细胞色素 c 氧化酶亚基 II 中铜离子识别肽序列的鉴定:理论和实验相结合的研究

已经使用多种实验和计算方法研究了源自细胞色素c氧化酶亚基 II 的金属离子结合环的表面暴露部分的五肽 NHSFM 对酶的双核紫色 CuA 中心成熟的作用。发现铜离子形成具有~10 4  M -1至10 5  M -1的结合常数的五肽的1:1复合物,其中揭示了来自2型铜中心的肽的4配体配位。金属肽的 pH 依赖性与\({\text{p}}K_{{\text{a}}}\)~ 10 表明 N 端胺的去质子化。EXAFS 研究以及金属-肽复合物的 DFT 计算揭示了金属-配体键距的 pH 依赖性变化。从 TDDFT 研究计算的金属肽的光谱性质与实验结果一致。受限分子动力学 (RMD) 模拟表明天冬酰胺 (N) 侧链中的羰基氧与组氨酸 (H)、蛋氨酸 (M) 和天冬酰胺 (N) 的末端胺以外的水分子在扭曲的方形平面几何形状中协调Cu-NHSFM。对金属肽的骨架距离和 B 因子的分析表明,在与金属离子结合时,肽骨架变得更加紧凑和刚性。

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更新日期:2021-04-30
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