Hemoglobin–ligand binding: Understanding Hb function and allostery on atomic level

The major physiological function of hemoglobin (Hb) is to bind oxygen in the lungs and deliver it to the tissues. This function is regulated and/or made efficient by endogenous heterotropic effectors. A number of synthetic molecules also bind to Hb to alter its allosteric activity. Our purpose is to review the current state of Hb structure and function that involves ensemble of tense and relaxed hemoglobin states and the dynamic equilibrium of the multistate due to the binding of endogenous heterotropic or synthetic allosteric effectors. The review also discusses the atomic interactions of synthetic ligands with the function or altered allosteric function of Hb that could be potentially harnessed for the treatment of diseases. This article is part of a Special Issue entitled: Protein Structure and Function in the Crystalline State.

Research Highlights► Hemoglobin structure and function involves ensemble of tense and relaxed states. ► Effectors can bind to the same site in Hb but produce opposite allosteric effects. ► Aromatic aldehydes can increase the fraction of the more soluble oxygenated sickle Hb. ► Allosteric effectors of Hb can increase oxygen delivery to tissues. ► αArg141, βTrp37 and G α-helix residues are important in Hb quaternary constraint.