Specific ligand binding on genetic variants of human alpha1-acid glycoprotein studied by circular dichroism
Ilona Fitos1, Júlia Visy, Ferenc Zsila
1Department of Molecular Pharmacology, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, P.O. Box 17, H-1525, Budapest, Hungary
Abstract:
Human alpha1-acid glycoprotein displays genetic polymorphism. Different drug binding properties of the two main genetic products (F1-S and A variants) have been demonstrated. In search for specific circular dichroism (CD) probes, dicumarol and acridine orange were found to specifically bind to the F1-S and A variants, respectively. Dicumarol binding to the F1-S variant produced induced Cotton effects originating from the favored chiral conformation of the bound label. Acridine orange gave induced biphasic Cotton effects due to chiral intermolecular exciton interaction between label molecules bound to the A variant. Displacement of the CD probes by specific marker ligands was demonstrated. The induced CD spectrum of dicumarol was found to change sign in the presence of imipramine, as a manifestation of high-affinity ternary complex formation on the F1-S variant.
More Related Videos
Related Concept Videos
Ligand Binding and Linkage
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Gene Families
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Cooperative Allosteric Transitions


