Circular Dichroism Spectroscopic Detection of Ligand Binding Induced Subdomain IB Specific Structural Adjustment of Human Serum Albumin

This work demonstrates for the first time that binding of various compounds within subdomain 113 of human serum albumin (HSA) provokes characteristic changes in the near-UV circular dichroism (CD) spectrum of the protein. It can be inferred from the spectroscopic features of difference ellipticity signals and from CD displacement experiments that tyrosine residues located in subdomain IB are the source of the observed spectral alterations. It is proposed that inclusion of some ligand molecules (bile adds, dehydroepiandrosterone sulfate, steroidal terpenes, fatty acids, ibuprofen, and gemfibrozil) into the pocket of subdomain IB disrupts the Tyr138-Tyr161 interhelical pi,pi stacking interaction, which is reflected in the CD spectrum. This phenomenon can be utilized for the CD detection of subdomain IB specific binding of endo- as well as exogenous agents and to study the drug binding associated local conformational adaptation of the HSA molecule.