Question

How is the binding of HPRG to heparin dependent on pH? Give structural reasons for the binding dependence. The structure of heparin is shown in Figure 2.2. NOTE: Figure 2.1 also serves as a titration curve for the His residues in HPRG–what is the pKR for these residues? Explain.

Answer 1

Since heparin is negatively charged, HPRG will bind to heparin more effectively if the HPRG is apositively charged. The pK of histidine is around 6.0. Below this pH, histidine is protonated andis thus positively charged, and the binding of heparin to HPRG is high. But as the pH increases,the histidines become unprotonated and lose their positive charge and bind to the heparin lesseffectively. Thus binding of HPRG to heparin decreases as pH increases.