Premium
A potential determinant of enhanced crystallization of HbC: spectroscopic and functional evidence of an alteration in the central cavity of oxyHbC
Author(s) -
Hirsch Rhoda Elison,
Rybicki Anne C.,
Fataliev Nazim A.,
Lin Margaret J.,
Friedman Joel M.,
Nagel Ronald L.
Publication year - 1997
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1997.2483062.x
Subject(s) - crystallization , chemistry , biophysics , medicine , biology , organic chemistry
The structural basis of the crystallizing tendencies of oxyHbC (β6Glu → Lys), that produces haemolytic anaemia in homozygotes, is unknown. Using a fluorescent organic phosphate analogue (8‐hydroxy‐1,3,6‐pyrenetrisulphonate), and conventional oxygen equilibrium studies, data suggest that the binding of inositolhexaphosphate (IHP) to oxyHbC differs from HbA, indicating perturbations of the oxyHbC central cavity, which was predicted from our earlier spectroscopic findings. To define the relationship between this conformational change in oxyHbC and its tendency to crystallize, the effect of four central cavity ligands on the crystallization rate was studied: a peptide containing 11 residues from the N‐terminal portion of band 3, the full cytoplasmic domain of band 3, 2,3‐diphosphoglycerate and IHP. OxyHbC crystallization was accelerated by all these central cavity ligands and not by the appropriate controls. These central cavity changes become an excellent candidate for the dramatic increase in the crystallization rate of oxyHbC.