A POTENTIAL DETERMINANT OF ENHANCED CRYSTALLIZATION OF HBC - SPECTROSCOPIC AND FUNCTIONAL EVIDENCE OF AN ALTERATION IN THE CENTRAL CAVITY OF OXYHBC

The structural basis of the crystallizing tendencies of oxyHbC (beta 6 Glu --> Lys), that produces haemolytic anaemia in homozygotes, is unkn own. Using a fluorescent organic phosphate analogue (8-hydroxy-1,3,6-p yrenetrisulphonate), and conventional oxygen equilibrium studies, data suggest that the binding of inositolhexaphosphate (IHP) to oxyHbC dif fers 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 residue s from the N-terminal portion of band 3, the full cytoplasmic domain o f band 3, 2,3-diphosphoglycerate and IHP. OxyHbC crystallization was a ccelerated by all these central cavity ligands and not by the appropri ate controls. These central cavity changes become an excellent candida te for the dramatic increase in the crystallization rate of oxyHbC.