Porphyrin-Mediated Photoinduced Conformational Changes To Human Serum Albumin At Physiological And Acidic Ph

Many of the biological and non-biological roles and uses of protoporphyrin-IX (PPIX) depend on its ability to bind large macromolecules such as human serum albumin (HSA). HSA is relevant to both biomedical and technological applications of PPIX (both free-base and metal), and its binding site for PPIX-derivatives is well established. Once bound, Heme (FePPIX) has be shown capable of transiently bestowing altered ligand-binding and pseudo-enzymatic properties to HSA that could be linked to biological functions. The irradiation of PPIX non-covalently bound to Beta-Lactoglobulin (BLG) is known to produce protein conformational changes that appear to be pH-dependent due to BLG's intrinsic conformational transitions. These processes have not been extensively studied in non-physiological pH conditions for FePPIX or PPIX bound to HSA. This study implemented a combination of optical methods and computational simulations to compare the binding characteristics of hemin and PPIX to HSA as well as examine the structural effects of low-dose irradiation of the ligand on the protein at different pH. Spectroscopic data suggests that irradiation of the porphyrins’ Soret band, when bound to HSA, is capable of modifying the globular protein structure by direct charge transfer mechanisms at both physiological and acidic pH conformations. Computational docking simulations predict lower free energy of binding for PPIX than for heme.