Comparative studies of the interaction of human and bovine platelet factor 4 with heparin using histidine NMR resonances as spectroscopic probes.
The pKa 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 1H NMR spectroscopy. The 1H NMR resonance of His-38 of bovine platelet factor 4 which exhibits the lower pKa value is perturbed upon heparin binding to a greater degree than the resonance of His-50. Human platelet factor 4 contains the homologous residues His-23 and His-35. The pKa values of the two histidine residues of human platelet factor 4 are 5.3 and 6.4. The 1H NMR resonance of the histidine of human platelet factor 4 exhibiting the lower pKa value also is perturbed upon heparin binding to a greater degree than the histidine resonance exhibiting the higher pKa, thereby suggesting comparable heparin-protein interactions in bovine and human platelet factor 4.
Department of Chemistry and Biochemistry, University of Windsor, Ontario, Canada.
C J
CJ
Talpas
L
L
Lee
D000818:Animals; D002417:Cattle; D004347:Drug Interactions; D006493:Heparin / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010978:Platelet Factor 4 / Q000737:chemistry*
D010978:Platelet Factor 4; D006639:Histidine; D006493:Heparin