Substrate binding modifies the hinge bending characteristics of human 3-phosphoglycerate kinase: A molecular dynamics study

Zoltan Palmai, Laurent Chaloin, Corinne Lionne, Judit Fidy, David Perahia, Erika Balog

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

3-Phosphogycerate kinase (PGK) is a two domain enzyme, with a binding site of the 1,3-bisphosphoglycerate on the N-domain and of the ADP on the C-domain. To transfer a phosphate group the enzyme has to undergo a hinge bending motion from open to closed conformation to bring the substrates to close proximity. Molecular dynamics simulation was used to elucidate the effect of ligand binding onto the domain motions of this enzyme. The simulation results of the apo form indicate a hinge bending motion in the ns timescale while the time period of the hinge bending motion of the complex form is clearly over the 20 ns simulation time. The apo form exhibits several hinge points that contribute to the hinge bending motion while upon binding the ligands, the hinge bending becomes strictly restrained with one dominant hinge point in the vicinity of the substrates. At the same time, ligand binding results in an enhanced correlation of internal domain motions.

Original languageEnglish
Pages (from-to)319-329
Number of pages11
JournalProteins: Structure, Function and Bioinformatics
Volume77
Issue number2
DOIs
Publication statusPublished - Nov 1 2009

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Keywords

  • Correlation of motions
  • Hinge bending
  • Human PGK
  • Molecular dynamics
  • Substrate binding

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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