Allosteric interpretation of the measurement of cooperative free energy in cyanomethemoglobin.

The experimentally resolved cooperative energies in partially ligated cyanomethemoglobin [F. R. Smith & G. K. Ackers (1985) Proc. Natl. Acad. Sci. USA 82, 5347-5351] have been compared with the predictions of an allosteric description of hemoglobin. A pattern of energetics similar to that observed (a "combinatorial switch") arises naturally from such an analysis using parameters in excellent agreement with other determinations. Although the energies for 2 of the 10 ligation states (namely, doubly ligated asymmetric tetramers) differ from the predictions, the remaining 8 of the 10 states exhibit excellent quantitative agreement with an allosteric description. This explains the discrepancy between previous analyses, which had found cyanomethemoglobin to be allosteric, and provides support for the basic allosteric concept that quaternary structure is the primary modifier for ligand affinity in hemoglobin.