title: R-state hemoglobin bound to heterotropic effectors: models of the DPG, IHP and RSR13 binding sites.
abstract: We performed a docking study followed by a 500-ps molecular dynamics simulation of R-state human adult hemoglobin (HbA) complexed to different heterotropic effectors [2,3-diphosphoglycerate (DPG), inositol hexaphosphate (IHP), and 2-[4-[(3,5-dichlorophenylcarbamoyl)-]methyl]-phenoxy]-2-methylpropionic acid (RSR13)) to propose a molecular basis for recently reported interactions of effectors with oxygenated hemoglobin. The simulations were carried out with counterions and explicit solvation. As reported for T-state HbA, the effector binding sites are also located in the central cavity of the R-state and differ depending on effector anionic character. DPG and IHP bind between the alpha-subunits and the RSR13 site spans the alpha1-, alpha2- and beta2-subunits. The generated models provide the first report of the molecular details of R-state HbA bound to heterotropic effectors.
authors.affiliation: Department of Biophysics and Radiation Biology and MTA-SE Research Group for Biophysics, Faculty of Medicine, Semmelweis University, P.O. Box 263, H-1444 Budapest, Hungary. laberge@puskin.sote.hu
authors.forename: Monique
authors.initials: M
authors.lastname: Laberge
authors.forename: Istvan
authors.initials: I
authors.lastname: Kövesi
authors.forename: Takashi
authors.initials: T
authors.lastname: Yonetani
authors.forename: Judit
authors.initials: J
authors.lastname: Fidy
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism*; D001665:Binding Sites; D004163:Diphosphoglyceric Acids / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D010833:Phytic Acid / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism*
chemical_list: D000814:Aniline Compounds; D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D011422:Propionates; D010833:Phytic Acid; C067396:efaproxiral