TY - JOUR
T1 - A potential determinant of enhanced crystallization of HbC
T2 - Spectroscopic and functional evidence of an alteration in the central cavity of oxyHbC
AU - Hirsch, Rhoda Elison
AU - Rybicki, Anne C.
AU - Fataliev, Nazim A.
AU - Lin, Margaret J.
AU - Friedman, Joel M.
AU - Nagel, Ronald L.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
KW - Band 3
KW - Crystallization kinetics
KW - Diphosphoglyceric acid
KW - Fluorescence
KW - HbC
UR - http://www.scopus.com/inward/record.url?scp=0030929566&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030929566&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2141.1997.2483062.x
DO - 10.1046/j.1365-2141.1997.2483062.x
M3 - Article
C2 - 9332311
AN - SCOPUS:0030929566
SN - 0007-1048
VL - 98
SP - 583
EP - 588
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 3
ER -