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The fact that the combination of one molecule of ligand with a macromolecule can influence the combination of another, the same or different, has been known for a long time, and the idea that the effect has its origin in conformational changes in the macromolecule was proposed more than a decade ago (Wyman, 1948; Wyman and Allen, 1951). The original observations were on hemoglobin, but it seemed clear that the phenomenon must be a general one in multifunctional molecule. This has now been amply demonstrated by the work of a number of investigators on a variety of proteins, some of which is reported in other contributions to this volume.
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Jeffries Wyman (1963) studied this question.
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