Subdomain IB is the third major drug binding region of human serum albumin: toward the three-sites model.

TitleSubdomain IB is the third major drug binding region of human serum albumin: toward the three-sites model.
Publication TypeJournal Article
Year of Publication2013
AuthorsZsila, F
JournalMol Pharm
Volume10
Issue5
Pagination1668-82
Date Published2013 May 6
ISSN1543-8392
KeywordsAllosteric Site, Biliverdine, Binding Sites, Binding, Competitive, Circular Dichroism, Fatty Acids, Hemin, Humans, Ligands, Models, Molecular, Pharmaceutical Preparations, Protein Structure, Tertiary, Serum Albumin, Spectrophotometry
Abstract

According to the conventional view, noncovalent association of small molecules with human serum albumin (HSA) occurs principally at the so-called Sudlow's sites located in subdomain IIA and IIIA. By employing a circular dichroism (CD) spectroscopic approach, it is shown that biliverdin is the specific CD label of an additional drug binding area in subdomain IB. CD competition experiments disclosed the entrapment of a diverse assortment of acidic, neutral, and basic molecules within subdomain IB including anticancer agents (camptothecin, doxorubicin, daunorubicin, teniposide, suramin, tyrosine kinase inhibitors), anticoagulants (dicoumarol), various steroids (bile acids, carbenoxolone), nonsteroidal antiinflammatory drugs, natural substances (aristolochic acid, glycyrrhetinic acid), and synthetic dyes (methyl orange, azocarmine B). These finding imply that subdomain IB can be considered as the third major drug binding region of HSA featured with promiscuous ligand recognition ability. Additionally, subdomain IB is allosterically coupled with the Sudlow's sites, the ligand binding of which is shown to alter the HSA binding mode and affinity of biliverdin and hemin. Brief case studies are presented to illustrate how the evaluation of spectral changes of tetrapyrrole CD probes gains new insight into the HSA binding properties of endogenous as well as pharmaceutical compounds.

DOI10.1021/mp400027q
Alternate JournalMol. Pharm.
PubMed ID23473402