title: Can a two-state MWC allosteric model explain hemoglobin kinetics?
abstract: We have analyzed the nanosecond-millisecond kinetics of ligand binding and conformational changes in hemoglobin. The kinetics were determined from measurements of precise time-resolved optical spectra following nanosecond photodissociation of the heme-carbon monoxide complex. To fit the data, it was necessary to extend the two-state allosteric model of Monod, Wyman, and Changeux (MWC) to include geminate ligand rebinding and nonexponential tertiary relaxation within the R quaternary structure. Considerable simplification of the model is obtained by using a linear free energy relation for the rates of quaternary transitions, and by incorporating concepts from recent studies on the physics of geminate rebinding and conformational changes in myoglobin. The model, described by 85 coupled differential equations, quantitatively explains a demanding set of complex kinetic data. Moreover, with the same set of kinetic parameters it simultaneously fits the equilibrium data on ligand binding and the distribution of ligation states. The present results, together with those from single-crystal oxygen binding studies, indicate that the two-state MWC allosteric model has survived its most critical tests.
authors.affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892-0520, USA.
authors.forename: E R
authors.initials: ER
authors.lastname: Henry
authors.forename: C M
authors.initials: CM
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Hofrichter
authors.forename: W A
authors.initials: WA
authors.lastname: Eaton
mesh_terms: D000495:Allosteric Site; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D009010:Monte Carlo Method; D010782:Photolysis; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013053:Spectrophotometry / Q000706:statistics & numerical data
chemical_list: D006454:Hemoglobins; D008024:Ligands