Structural Evidence of Perfluorooctane Sulfonate Transport by Human Serum Albumin

Abstract

Perfluorooctane sulfonate (PFOS) is a man-made fluorosurfactant and globally persistent organic pollutant. PFOS is mainly distributed in blood with a long half-life for elimination. PFOS was found mainly bound to human serum albumin (HSA) in plasma, the most abundant protein in human blood plasma, which transports a variety of endogenous and exogenous ligands. However, the structural basis of such binding remains unclear. Here, we report the crystal structure of the HSA−PFOS complex and show that PFOS binds to HSA at a molar ratio of 2:1. In addition, PFOS binding renders the HSA structure more compact. Our results provide a structural mechanism to understand the retention of surfactants in human serum. P erfluorooctane sulfonate (PFOS) (Supporting Information, Figure S1) is a stable chemical with high surface activity, high thermal and acid resistance, and with both hydroand lipophobic properties. PFOS have been used in a wide range of industrial and commercial applications since 1950s.

Exploring the Use of Molecular Docking to Identify Bioaccumulative Perfluorinated Alkyl Acids (PFAAs)

“…The second, 4E99, is for PFOS bound to HSA, and is the only crystal structure available for HSA binding with a PFAA. 31 As Luo et al (2012) showed in their study, HSA undergoes substantial conformational changes when binding with PFOS, becoming more compact. We then used the "align" command in PyMol 43 to measure the root-mean-square distance (RMSD) between all 31 structures, and selected a third structure to represent the midpoint between the conformations of 1E7G and 4E99.…”

“…(2012), 31 we used their crystal structure of PFOS bound to HSA (PDB structure 4E99) for redocking. The root-mean-square deviation (RMSD) between the published crystal structure and the docked PFOS is calculated using the pairwise fitting procedure in PyMol.…”

“…In 2012, Luo et al published the first crystal structure of the HSA-PFOS complex. 31 This remains the only PFAS−protein complex that has been experimentally determined to date. They show two binding sites for PFOS: fatty acid site 3/4 (FA 3/4), which overlaps with SII, and fatty acid site 6 (FA 6), which is adjacent to Trp.…”

“…12 Therefore, a methodology for large-scale screening of protein-PFAS interactions has not yet been developed, though some initial work indicates that in-silico docking methods may hold promise. 28,31,34 Protein−ligand docking is an important tool in computeraided drug design, which predicts the interaction between a protein and a ligand both in terms of structure, to find likely binding modes, and energetics, to estimate binding affinity. 35 The protein and ligand are defined by their position (x, y, z, angles) and, for the flexible ligand, by the angles of each rotatable bond.…”

Zn2+‐Responsive Bimodal Magnetic Resonance Imaging and Fluorescence Imaging Agents and Their Interaction with Human Serum Albumin

“…[1,3] Meanwhile, HSA binding could improve the pharmacokinetics and enhance the half-life of imaging agents. [1,5] As a result, HSA binding is a promising approach to improve the performance of imaging agents.…”