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Crowding and the polymerization of sickle hemoglobin
Journal article

Crowding and the polymerization of sickle hemoglobin

Frank A Ferrone and Maria A Rotter
Journal of molecular recognition, v 17(5), pp 497-504
Sep 2004
PMID: 15362110

Abstract

Biopolymers - chemistry Thermodynamics Hemoglobin, Sickle - chemistry Anemia, Sickle Cell - metabolism Humans Kinetics Biopolymers - metabolism Hemoglobin, Sickle - metabolism Solutions - chemistry
Under physiological conditions, sickle hemoglobin, a natural mutant of human hemoglobin A with a surface hydrophobic valine in place of a negatively charged glutamic acid, polymerizes at high volume occupancy. Equilibrium solubility of sickle hemoglobin entails activity coefficients that can approach 10(3) at high concentrations. Polymerization occurs by homogeneous and heterogeneous nucleation mechanisms, which are both profoundly sensitive to crowding; homogeneous nucleation rates for example are enhanced by 10(10) when the initial concentration is augmented by 50% non-polymerizing hemoglobin. A molecular description of the reaction therefore entails substantial corrections for molecular crowding which are all very accurately described by excluded volume corrections, treating hemoglobin as a hard sphere with volume consistent with the molecular structure of the molecule, and involving no further adjustable parameters. These effects and the descriptions that rationalize this behavior are described.

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Web of Science research areas
Biochemistry & Molecular Biology
Biophysics
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