The evolutionary footprint of histidine in hemoglobin and myoglobin: an implication towards their function

IF 2.8 3区化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biological Inorganic Chemistry Pub Date : 2026-04-13 DOI:10.1007/s00775-026-02147-y

Jayraj Biswas, Kauseki Dutta, Kakali Biswas, Raja Banerjee

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Abstract

Hemoglobin and myoglobin are essential oxygen-binding proteins whose structural integrity is critical for proper function. This study performs atomic-level comparisons of wild-type and mutant forms to investigate how specific mutations impact oxygen-binding affinity. Substitution of the proximal histidine, responsible for coordinating the iron atom in the heme group, with tyrosine results shortening of bond distances in haemoglobin, while Van der Waals clashes in myoglobin; impairing function of both. Other mutations (α125Leu > Pro, β34Val > Asp, β63His > Tyr, β92His > Asn) compromise the protein stability by disrupting inter-chain hydrogen bonds and helical structures, reducing oxygen-binding efficiency. Cross-species comparisons, from Actinopterygii to Mammalia, underscore strong conservation of these critical residues essential for preserving the indispensable structural and functional integrity of these proteins since the dawn of their existence.

Graphical abstract

Since the dawn of its existence high conservation of sequences especially histidine for maintaining the functionality of hemoglobin and myoglobin.

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组氨酸在血红蛋白和肌红蛋白中的进化足迹：对其功能的暗示。

血红蛋白和肌红蛋白是必需的氧结合蛋白，其结构完整性对正常功能至关重要。本研究进行了野生型和突变形式的原子水平比较，以研究特异性突变如何影响氧结合亲和力。用酪氨酸取代血红蛋白中负责协调铁原子的近端组氨酸导致血红蛋白中的键距缩短，而在肌红蛋白中发生范德华冲突；损害两者的功能。其他突变（α125Leu > Pro, β34Val > Asp, β63His > Tyr, β92His > Asn）通过破坏链间氢键和螺旋结构，降低氧结合效率而破坏蛋白质的稳定性。跨物种比较，从放线翼目到哺乳动物，强调了这些关键残基的强保守性，这些残基自存在之初就对保持这些蛋白质必不可少的结构和功能完整性至关重要。

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.