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

Monique Laberge, Istvan Kövesi, Takashi Yonetani, J. 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

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2,3-Diphosphoglycerate
Phytic Acid
Hemoglobins
Binding Sites
Isobutyrates
Solvation
Molecular Dynamics Simulation
Molecular dynamics
Computer simulation
efaproxiral

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

R-state hemoglobin bound to heterotropic effectors : Models of the DPG, IHP and RSR13 binding sites. / Laberge, Monique; Kövesi, Istvan; Yonetani, Takashi; Fidy, J.

In: FEBS Letters, Vol. 579, No. 3, 31.01.2005, p. 627-632.

Research output: Contribution to journalArticle

Laberge, Monique ; Kövesi, Istvan ; Yonetani, Takashi ; Fidy, J. / R-state hemoglobin bound to heterotropic effectors : Models of the DPG, IHP and RSR13 binding sites. In: FEBS Letters. 2005 ; Vol. 579, No. 3. pp. 627-632.
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