Here we report on the excited-state behavior in terms of the excited-state proton-transfer (ESPT) reaction as well as the ground-state acid base property of pyranine [8-hydroxypyrene-1,3,6-trisulfonate (HPTS)] in the presence of an enzymatic protein, human lysozyme (LYZ). HPTS forms a 1:1 ground-state complex with LYZ having the binding constant K-BH = (1.4 +/- 0.05) x 10(4) M-1, and its acid base equilibrium gets shifted toward the deprotonated conjugate base (RO-), resulting in a downward shift in pKa. This suggests that the conjugate base (RO-) is thermodynamically more favored over the protonated (ROH) species inside the lysozyme matrix, resulting in an increased population of the deprotonated form. However, for the release of the proton from the excited photoacid, interestingly, the rate of proton transfer gets slowed down due to the "slow" acceptor biological water molecules present in the immediate vicinity of the fluorophore binding region inside the protein. The observed ESPT time constants, similar to 140 and similar to 750 ps, of protein-bound pyranine are slower than in bulk aqueous media (similar to 100 ps, single exponential). The molecular docking study predicts that the most probable binding location of the fluorophore is in a region near to the active site of the protein. Here we also report on the effect of external electrolyte (NaCl) on the reverse modulation of ground-state prototropy as well as the ESPT process of the protein-bound pyranine. It is found that there is a dominant role of electrostatic forces in the HPTS LYZ interaction process, because an increase in ionic strength by the addition of NaCl dislodges the fluorophore from the protein pocket to the bulk again. The study shows a considerably different perspective of the perturbation offered by the model macromolecular host used, unlike the available literature reports on the concerned photoacid.