Study on the Interaction Between Trimethoprim and Human Serum Albumin by Spectroscopic and Molecular Modeling Methods

Abstract

ABSTRACT The interaction between trimethoprim (TMP) and human serum albumin (HSA) was studied by fluorescence spectroscopy, UV-vis absorption spectroscopy, FT-IR spectroscopy, and molecular modeling. The experimental results showed that the fluorescence intensity of HSA was quenched by TMP in a static quenching mechanism. HSA had one binding site in subdomain IIA for TMP, which was verified by the displacement experiment. Thermodynamic parameters indicated that hydrogen bonds and van der Waals force played a major role during the interaction. The distance between TMP and HSA was estimated to be 1.67 nm based on Föster's theory. Synchronous fluorescence spectra indicated that TMP can change the conformation of HSA, resulting in increased polarity around Trp residues. According to FT-IR, the α-helix content of HSA was reduced from 51.4% to 46.7%, and the random coil was increased about 5.2%. The molecular modeling result showed that N3 and N4 of TMP mainly interact with Cys 245 and Gly 248 predominantly through hydrogen bonds. Hydrophobic interactions (C1 and C4 of TMP with Cys 200; C14 of TMP with His 242; etc.) and other forces (O3, C2, C11, and C13 of TMP with Gln196; C12 of TMP with His 242 and Arg 257) were also presented.