Interaction of inhibitors with potential cytoskeleton related protein phosphatases

  • Д. А. Самофалова
  • П. А. Карпов
  • Я. Б. Блюм


Aim. Recent studies revealed significant structure differences in phosphatase inhibitors suppressing serine/threonine and tyrosine-specific protein phosphatases (PPs), involved in MT-cytoskeleton structure and dynamics regulation. The matter of current study was revision of known inhibitors of "cytoskeletal" PPs, as well as the study of specific features of ligand-protein interaction. Methods. Deposited in RCSB PDB ligand-protein complexes were analyzed using ZINCPharmer, PoseView, CCDC Relibase, PRODRAG, LigandScout, Gromacs (MM+, CHARMM) and BIOVIA DS Visualizer. Results. Were established structural features of ligand-protein interactions for 32-x PDB structures: 23 for PPPs in complex with NHC, ENL, OKA, PRD_000212, PRD_000215, CYU, PRD_000214, PRD_000213, E7B, XT1/XT2 and 9 for PTPs in complex with 761, OAI, 878, OBA, 825; DBD, PSY, ZYZ, PVS. Conclusions. It was found that binding of PP-inhibitors with target proteins generally occurs with the assistance of metal ion(s) and water molecule(s). Also, it was created local database of PP-inhibitors with necessary for subsequent bioinformatic research: topology, biological activity and natural conformation.

Keywords: protein phosphatase inhibitors, PPP, PTP, chemoinformatics.