A Comprehensive Structural Overview of p38α Mitogen-Activated Protein Kinase in Complex with ATP-Site and Non-ATP-Site Binders

ChemMedChem. 2018 Jan 8;13(1):7-14. doi: 10.1002/cmdc.201700636. Epub 2017 Dec 18.

Abstract

Herein we review all the currently available ATP-site and non-ATP-site ligands bound to p38α mitogen-activated protein kinase (MAPK) available in the RCSB Protein Data Bank (PDB). The co-crystallized inhibitors have been classified into different families according to their experimental binding mode and chemical structure, and the ligand-protein interactions are discussed using the most representative compounds. This systematic structural analysis could provide some take-home lessons for drug discovery programs aimed at the rational identification and optimization of new p38α MAPK inhibitors.

Keywords: crystal structures; inhibitors; kinases; ligand-protein interactions; p38α MAPK.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism*
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Ligands
  • Mitogen-Activated Protein Kinase 14 / chemistry
  • Mitogen-Activated Protein Kinase 14 / metabolism*
  • Molecular Dynamics Simulation
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Structure, Tertiary

Substances

  • Ligands
  • Protein Kinase Inhibitors
  • Adenosine Triphosphate
  • Mitogen-Activated Protein Kinase 14