CAN A 2-STATE MWC ALLOSTERIC MODEL EXPLAIN HEMOGLOBIN KINETICS

We have analysed the nanosecond-millisecond kinetics of ligand binding and conformational changes in hemoglobin. The kinetics were determine d 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 mode l of Monod, Wyman, and Changeux (MWC) to include geminate ligand rebin ding and nonexponential tertiary relaxation within the R quaternary st ructure. 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 explai ns a demanding set of complex kinetic data. Moreover, with the same se t of kinetic parameters it simultaneously fits the equilibrium data on ligand binding and the distribution of ligation states. The present r esults, together with those from single-crystal oxygen binding studies , indicate that the two-state MWC allosteric model has survived its mo st critical tests.