title: Identification of possible kinetically significant anion-binding sites in human serum transferrin using molecular modeling strategies.
abstract: Certain anions have been shown experimentally to influence the rate of iron release from human serum transferrin (HST), implying the existence of one or more allosteric kinetically significant anion-binding (KISAB) sites on or near the surface of the protein. A rank-ordered selection of potential HST KISAB sites has been obtained using a novel three-stage molecular modeling strategy. The crystal structure of HST (1A8E.pdb) was first subjected to a heuristic analysis, in which positively charged and hydrogen-bonding residues on or near the surface of the protein were identified. In this stage, a preliminary electrostatic potential map was also calculated, yielding six preliminary sites. Next, energy-grid calculations were conducted in order to identify anion-protein interaction energy minima, which resulted in the inclusion of three additional sites. Finally, three anions already shown experimentally to demonstrate varied effects on HST iron-release kinetics were placed at each potential site; molecular dynamics and molecular mechanics calculations were performed in order to elucidate the hydrogen-bonding environment around each anion of the protein as well as to calculate anion-protein-binding energies.
authors.affiliation: Department of Chemistry and Biochemistry, University of Missouri- St. Louis, 8001 Natural Bridge Road, St. Louis, MO 63121, USA.
authors.forename: Elizabeth Ambrose
authors.initials: EA
authors.lastname: Amin
authors.forename: Wesley R
authors.initials: WR
authors.lastname: Harris
authors.forename: William J
authors.initials: WJ
authors.lastname: Welsh
mesh_terms: D000838:Anions / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002712:Chlorides / Q000737:chemistry / Q000378:metabolism; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D010472:Perchlorates / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D014168:Transferrin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000838:Anions; D002712:Chlorides; D005290:Ferric Compounds; D010472:Perchlorates; D011994:Recombinant Proteins; D012997:Solvents; D013431:Sulfates; D014168:Transferrin