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

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.