The structure--function relationship of hemoglobin in solution at atomic resolution.
Date of Original Version
Abstract or Description
Hemoglobin (Hb) is an essential component of the circulatory system of vertebrates. Its chief physiological function is to transport oxygen from the lungs to the tissues. For reviews of the structure−function relationship in hemoglobin, see Dickerson and Geiss,1 Ho,2 and Ho and Lukin.3 Human normal adult hemoglobin (Hb A) is one of the most studied proteins and has served as a model or paradigm for multimeric allosteric proteins. Hemoglobin is a useful system for testing a basic premise of structural biology, which holds that the functional properties of a protein can be explained in terms of its structure and dynamic behavior on the atomic scale. Since the first crystal structures of Hb A were determined by Perutz and colleagues in the 1960s, extensive efforts have been devoted to elucidating the relationship of hemoglobin's structure with its physiologically important properties, including the cooperative binding of oxygen, and the control of oxygen affinity by pH (the Bohr effect) and allosteric effectors such as 2,3-bisphosphoglycerate (2,3-BPG). Despite these efforts, the detailed structural basis of these properties is not fully understood, and some aspects remain controversial. Much of our current understanding of Hb A has been obtained with reference to X-ray crystal structures. However, since the protein performs its physiological functions in the solution state, it is useful to investigate its structure−function relationships in solution, using techniques including infrared, resonance Raman, and nuclear magnetic resonance (NMR) spectroscopies.
Chemical reviews, 104, 3, 1219-1230.