Computational modelling of the redistribution of copper isotopes by proteins in the liver†,Metallomics

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Computational modelling of the redistribution of copper isotopes by proteins in the liver†
Metallomics ( IF 2.9 ) Pub Date : 2017-11-15 00:00:00 , DOI: 10.1039/c7mt00248c
Alexander Tennant _{1,

2,

3,

4} , Arvi Rauk _{1,

3,

4,

5} , Michael E. Wieser _{1,

2,

3,

4}

Affiliation

Changes in the stable isotope composition of copper in blood serum as a result of biological processes in the liver were quantified as coupled equilibrium fractionation processes. The model used calculated reduced partition function ratios corresponding to interactions involving individual proteins using Density Functional Theory. This quantified the effect that each process had on the redistribution of copper isotopes in the liver. It was not possible to calculate the reduced partition function of CTR1 as a high resolution crystal structure of its copper binding domains are unavailable at the time of writing, and an optimization process was used to estimate the reduced partition function of CTR1 and constrain the possible isotopic fractionation associated with interactions involving CTR1 independent of direct DFT calculations and assumptions of its structure. The exchange of copper between ceruloplasmin and ATP7B has the most significant impact on the copper isotopic composition of blood serum. The model calculation for the isotopic composition of ceruloplasmin and albumin are δ⁶⁵Cu = (−0.54 ± 0.10)‰ and δ⁶⁵Cu = (0.08 ± 0.25)‰ respectively, assuming that serum is 90% ceruloplasmin and 10% albumin using a measured δ⁶⁵Cu of serum of (0.52 ± 0.08)‰. The model also predicts that the isotopic composition of the tri-nuclear binding motif of ceruloplasmin may be relatively depleted in the lighter isotope of Cu compared to the other copper binding sites by as much as −1.08 ± 0.45‰.

中文翻译：

肝脏中蛋白质对铜同位素的重新分布的计算模型†

由于肝脏中的生物学过程，血清中铜的稳定同位素组成的变化被量化为耦合平衡分馏过程。该模型使用密度泛函理论计算了对应于涉及单个蛋白质相互作用的减少的分区功能比率。这量化了每个过程对肝脏中铜同位素重新分布的影响。由于撰写本文时无法获得其铜结合域的高分辨率晶体结构，因此无法计算出降低的CTR1的分配函数，并使用了优化过程来估算CTR1的简化分配函数，并限制与CTR1相互作用相关的可能的同位素分离，而与直接DFT计算及其结构假设无关。铜蓝蛋白和ATP7B之间的铜交换对血清铜同位素组成影响最大。铜蓝蛋白和白蛋白的同位素组成的模型计算为δ ⁶⁵的Cu =（-0.54±0.10）‰和δ ⁶⁵的Cu =分别（0.08±0.25）‰，假设血清为90％血浆铜蓝蛋白和白蛋白使用测量10％δ ⁶⁵的Cu（0.52±0.08）血清的‰ 。该模型还预测，与其他铜结合位点相比，铜的轻同位素中铜蓝蛋白的三核结合基序的同位素组成可能相对减少了-1.08±0.45‰。

更新日期：2017-11-15

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