CO ligation intermediates and the mechanism of hemoglobin cooperativity - PubMed (original) (raw)

. 1999 Jan 29;274(5):2605-8.

doi: 10.1074/jbc.274.5.2605.

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CO ligation intermediates and the mechanism of hemoglobin cooperativity

M Perrella et al. J Biol Chem. 1999.

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Abstract

Direct experimental resolution of the ligation intermediates for the reaction of human hemoglobin with CO reveals the distribution of ligated states as a function of saturation. At low saturation, binding of CO occurs with slightly higher affinity to the beta chains, but pairwise interactions are more pronounced between the alpha chains. At high saturation, the two chains tend to behave identically. The sequence of CO ligation reconstructed from the distribution of intermediates shows that the overall increase in CO affinity is 588-fold, but it is not distributed uniformly among the ligation steps. The affinity increases 16.5-fold in the second ligation step, 4.6-fold in the third ligation step, and 7.7-fold in the fourth ligation step. This pattern and the detailed distribution of ligated states cannot be immediately reconciled with the predictions of either the concerted allosteric model of Monod-Wyman-Changeux or the sequential model of Koshland-Nemethy-Filmer and underscore a more subtle mechanism for hemoglobin cooperativity.

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