Investigation of 15-hydroxyprostaglandin dehydrogenase catalytic reaction mechanism by molecular dynamics simulations

J Mol Graph Model. 2018 Mar:80:190-196. doi: 10.1016/j.jmgm.2018.01.012.

Abstract

15-hydroxyprostaglandin dehydrogenase (15-PGDH) is a prostaglandin metabolizing enzyme that oxidizes the hydroxyl group at carbon 15 (C15). The aim of the present work is to propose the main amino acids that catalyze the reaction through studying the intermolecular interaction between the ligand and the enzyme inside the active site using molecular dynamics simulation (MD). Therefore, MD simulations for two 15-PGDH systems bound with a substrate (PGE2) or an inhibitor (compound 4) were performed to investigate the importance of ligand interaction on the behavior of amino acids in the active site. Findings from this work proposed the amino acids: Tyr151, Gln148 & Asn95 to act as a catalytic triad for the reaction as hydrogen bond interactions, dihedral rotation analysis and MM-GBSA free energy calculations revealed.

Keywords: 15-PGDH; MM-GBSA; Molecular docking; Molecular dynamics simulation; PGE(2).

MeSH terms

  • Binding Sites
  • Catalysis
  • Catalytic Domain
  • Dinoprostone / chemistry
  • Dinoprostone / metabolism
  • Hydrogen Bonding
  • Hydroxyprostaglandin Dehydrogenases / chemistry*
  • Hydroxyprostaglandin Dehydrogenases / metabolism
  • Ligands
  • Molecular Conformation
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation*
  • Oxidation-Reduction
  • Protein Binding
  • Quantitative Structure-Activity Relationship*

Substances

  • Ligands
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase
  • Dinoprostone