R-state hemoglobin bound to heterotropic effectors: Models of the DPG, IHP and RSR13 binding sites

Monique Laberge, Istvan Kövesi, Takashi Yonetani, Judit Fidy

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 α-subunits and the RSR13 site spans the α1-, α2- and β2-subunits. The generated models provide the first report of the molecular details of R-state HbA bound to heterotropic effectors.

Original languageEnglish
Pages (from-to)627-632
Number of pages6
JournalFEBS letters
Volume579
Issue number3
DOIs
Publication statusPublished - Jan 31 2005

Keywords

  • Allosteric effector
  • Docking
  • Hemoglobin A
  • Heterotropic effector
  • Molecular dynamics

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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