Previous mutational studies on Tyr42α variants as well as the current studies on the mutant hemoglobin αY42A show that the intersubunit interactions associated with Tyr42α significantly stabilize the α1β2 interface of the quaternary-T deoxyhemoglobin tetramer. However, crystallographic studies, UV and visible resonance Raman spectroscopy, CO combination kinetic measurements, and oxygen binding measurements on αY42A show that the intersubunit interactions formed by Tyr42α have only a modest influence on the structural properties and ligand affinity of the deoxyhemoglobin tetramer. Therefore, the α1β2 interface interactions associated with Tyr42α do not contribute significantly to the quaternary constraints that are responsible for the low oxygen affinity of deoxyhemoglobin. The slight increase in the ligand affinity of deoxy αY42A correlates with small, mutation-induced structural changes that perturb the environment of Trp37β, a critical region of the quaternary-T α1β2 interface that has been shown to be the major source of quaternary constraint in deoxyhemoglobin.
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