The effect of 2,3-diphosphoglycerate on the solubility of deoxyhemoglobin S

Archives of Biochemistry and Biophysics
W N PoillonJ A Walder

Abstract

Although highly charged polyanions, such as inositol hexaphosphate, have been clearly shown to decrease the solubility of deoxyhemoglobin S, the effect of 2,3-diphosphoglycerate (DPG), the endogenous allosteric effector within the red cell, has been more controversial. In this work we have compared the effect of DPG on the solubility of native deoxyhemoglobin S and a derivative in which the DPG binding site is blocked by cross-linking the two beta 82 lysine residues. At pH 6.6 and 30 degrees C the solubility of deoxyhemoglobin S was found to be decreased by 15% (i.e., from 18.8 to 16.0 g/dl) in the presence of saturating concentrations of DPG. Under the same conditions DPG had no effect on the solubility of the cross-linked derivative. This result establishes unequivocally that the binding of DPG within the beta cleft directly facilitates the polymerization of deoxyhemoglobin S. Under physiological conditions, the solubility of deoxyhemoglobin S was found to be decreased by 6% in the presence of an equimolar concentration of DPG. A solubility decrease of this magnitude is sufficient to enhance the tendency of SS cells to sickle and may exacerbate the clinical symptoms of sickle cell disease.

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Citations

Dec 21, 2010·Nature Medicine·Yujin ZhangYang Xia
Apr 4, 2013·Current Opinion in Hematology·Kaiqi Sun, Yang Xia
Mar 5, 2014·Hematology/oncology Clinics of North America·Martin K Safo, Gregory J Kato
May 29, 2012·Microbes and Infection·Yujin Zhang, Yang Xia
Oct 6, 2018·Acta Crystallographica. Section D, Structural Biology·Tanvi M DeshpandeMartin K Safo

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