title: Exploration of pH-dependent behavior of the anion receptor pocket of subdomain IIA of HSA: determination of effective pocket charge using the Debye-Hückel limiting law.
abstract: Protein-ligand electrostatic interaction can be looked upon as ion receptor-ligand interaction, and the binding cavity of protein can be either an anion or cation receptor depending on the charge of the guest. Here we focus on the exploration of pH-modulated binding of a number of anionic ligands, specific to the subdomain IIA cavity of HSA, such as carmoisine, tartrazine, cochineal red, and warfarin. The logarithm of the binding constant is found to vary linearly with the square-root of ionic strength, indicating applicability of the Debye-Hückel limiting law to protein-ligand electrostatic binding equilibrium, and concludes that the subdomain IIA cavity is an anion receptor. The present approach is very unique that one can calculate the effective charge of the protein-based anion receptor pocket, and the calculated charge has been found to vary between +1 and +3 depending on the pH and ligand itself. The study also indicates that in such cases of specific ligand binding the pocket charge rather than the overall or surface charge of the macromolecule seems to have a paramount role in determining the strength of interaction. For the first time, it is demonstrated that the Debye-Hückel interionic interaction model can be successfully applied to understand the protein-based receptor-ligand electrostatic interaction in general.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kharagpur , Kharagpur-721302, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Bolel
authors.forename: Shubhashis
authors.initials: S
authors.lastname: Datta
authors.forename: Niharendu
authors.initials: N
authors.lastname: Mahapatra
authors.forename: Mintu
authors.initials: M
authors.lastname: Halder
mesh_terms: D000838:Anions / Q000737:chemistry / Q000378:metabolism; D001391:Azo Compounds / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009282:Naphthalenesulfonates / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D055672:Static Electricity; D013645:Tartrazine / Q000737:chemistry / Q000378:metabolism*; D014859:Warfarin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000838:Anions; D001391:Azo Compounds; D008024:Ligands; D009282:Naphthalenesulfonates; D012709:Serum Albumin; D014859:Warfarin; C006671:azo rubin S; D013645:Tartrazine; C576297:ponceau 4R