COMPARATIVE-STUDIES OF THE INTERACTION OF HUMAN AND BOVINE PLATELET FACTOR-IV WITH HEPARIN USING HISTIDINE NMR RESONANCES AS SPECTROSCOPIC PROBES

The pK(a) values of His-38 and His-50 of the heparin-binding protein, bovine platelet factor 4, are 5.6 and 6.5, respectively, as determined by H-1 NMR spectroscopy. The H-1 NMR resonance of His-38 of bovine pl atelet factor 4 which exhibits the lower pK(a) value is perturbed upon heparin binding to a greater degree than the resonance of His-50. Hum an platelet factor 4 contains the homologous residues His-23 and His-3 5. The pK(a) values of the two histidine residues of human platelet fa ctor 4 are 5.3 and 6.4. The H-1 NMR resonance of the histidine of huma n platelet factor 4 exhibiting the lower pK(a) value also is perturbed upon heparin binding to a greater degree than the histidine resonance exhibiting the higher pK(a), thereby suggesting comparable heparin-pr otein interactions in bovine and human platelet factor 4.