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Crowding and the polymerization of sickle hemoglobin
Author(s) -
Ferrone Frank A.,
Rotter Maria A.
Publication year - 2004
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.698
Subject(s) - hemoglobin , polymerization , nucleation , chemistry , homogeneous , solubility , hemoglobin a , volume (thermodynamics) , chemical physics , chemical engineering , polymer chemistry , thermodynamics , organic chemistry , polymer , physics , engineering
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. Copyright © 2004 John Wiley & Sons, Ltd.