Is cooperative oxygen binding by hemoglobin really understood?
The enormous success of structural biology challenges the physical scientist. Can biophysical studies provide a truly deeper understanding of how a protein works than can be obtained from static structures and qualitative analysis of biochemical data? We address this question in a case study by presenting the key concepts and experimental results that have led to our current understanding of cooperative oxygen binding by hemoglobin, the paradigm of structure function relations in multisubunit proteins. We conclude that the underlying simplicity of the two-state allosteric mechanism could not have been demonstrated without novel physical experiments and a rigorous quantitative analysis.
Eaton
W A
WA
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA. eaton@helix.nih.gov
Henry
E R
ER
Hofrichter
J
J
Mozzarelli
A
A
D002627:Chemistry, Physical / Q000379:methods; D006454:Hemoglobins / Q000737:chemistry* / Q000266:history / Q000378:metabolism*; D049673:History, 20th Century; D007700:Kinetics; D008958:Models, Molecular; D008967:Molecular Biology / Q000379:methods; D009154:Mutation; D010100:Oxygen / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
D006454:Hemoglobins; D010100:Oxygen