Molecular interaction of PCB180 to human serum albumin: insights from spectroscopic and molecular modelling studies

Abstract

Polychlorinated biphenyls (PCBs) are potentially hazardous to the environment because of their chemical stability and biological toxicity. In this study, we identified the binding mode of a representative PCB180 to human serum albumin (HSA) using fluorescence and molecular dynamics (MD) simulation methods. PCB180 bound exactly at subdomain IIIA of HSA based on the fluorescence study along with site marker displacement experiments. PCB180 also induced conformational changes that were governed mainly by hydrophobic forces. MD studies and free energy calculations also made important contributions to the understanding of the effects of an HSA-PCB180 system on conformational changes. The simulations on binding behavior proved that PCB180 was located only in subdomain IIIA. Hydrophobic interactions dominated the mode of binding behavior. The results obtained using the two methods correlated well with each other. Our findings provide a framework for elucidating the mechanisms of PCB180-HSA binding, and may also help in further research on the transportation, distribution, and toxicity effects of PCBs when introduced into human blood serum.

Sulfation of Lower Chlorinated Polychlorinated Biphenyls Increases Their Affinity for the Major Drug-Binding Sites of Human Serum Albumin

“…47 Ligand-bound crystal structures for the 66.5kDa protein show the various drug-, fatty acid-, ion-, and heme-binding sites of HSA, 48 and many methods have been employed to determine binding parameters. 41, 49–51 In our present studies, we have measured the displacement of site-selective fluorescent probes from the two major drug-binding sites on HSA (i.e., Site I and Site II) as described by Sudlow et al 40 In this examination of LC-PCBs and their hydroxylated and sulfated metabolites, the displacement of: 5-dimethylamino-1-naphthalenesulfonamide (DNSA) for Site I and dansyl L-proline (DP) for Site II, shown in Figure 1, was used. 40 The displacement of these probes from their respective binding sites has been used to determine site-selectivity for ligands as well as to provide relative estimates of their binding affinities.…”

“…Previous studies on the binding of individual higher chlorinated PCB congeners to HSA found that binding occurred at Site II. 49, 50 The binding of PCB 153 and the PCB 180 to HSA was determined using a combination of intrinsic fluorescence, probe displacement and molecular modelling. It was determined that both compounds bound to a single site of HSA, Sudlow Site II, and that binding was dominated by hydrophobic interactions.…”

“…It was determined that both compounds bound to a single site of HSA, Sudlow Site II, and that binding was dominated by hydrophobic interactions. 49,50 Interestingly, a separate study of PCB 118, 126, and 153 found that these compounds bound with high affinity to Sudlow Site I, with no binding to Site II. 51 These seemingly contradictory conclusions may stem from the differences in the design of the studies.…”

Hydroxylated and sulfated metabolites of lower chlorinated PCBs bind with high affinity to human serum albumin and exhibit selective toxicity to neuronal cells

“…The results of these few studies, however, are sometimes contradictory. [163][164][165] Neurotoxic effects of PCB exposure…”

“…Previous studies on the binding of individual PCB congeners to HSA found that binding occurred at Site II. 163,165 One study, however, determined that binding occurred at Site I. 164 These seemingly contradictory conclusions stem from the differences in the studies.…”