Crystal structure of death-associated protein kinase 1 in complex with the dietary compound resveratrol

Takeshi Yokoyama*, Ryoya Suzuki, Mineyuki Mizuguchi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Death-associated protein kinase 1 (DAPK1) is a large multidomain protein with an N-terminal serine/threonine protein kinase domain. DAPK1 is considered to be a promising molecular target for the treatment of Alzheimer's disease (AD). In the present study, the inhibitory potency of resveratrol (RSV), a dietary polyphenol found in red wine, against the catalytic activity of DAPK1 was investigated. Kinetic and fluorescent probe competitive binding analyses revealed that RSV directly inhibited the catalytic activity of DAPK1 by binding to the ATP-binding site. Crystallographic analysis of DAPK1 in complex with RSV revealed that the A-ring of RSV occupied the nucleobase-binding position. Determination of the binding mode provided a structural basis for the design of more potent DAPK1 inhibitors. In conclusion, the data here clearly show that RSV is an ATP-competitive inhibitor of DAPK1, encouraging speculation that RSV may be useful for the development of AD inhibitors.

Original languageEnglish
Pages (from-to)131-138
Number of pages8
JournalIUCrJ
Volume8
DOIs
StatePublished - 2021

Keywords

  • Alzheimer's disease
  • DAPK1
  • Protein-drug interactions
  • Resveratrol

ASJC Scopus subject areas

  • General Chemistry
  • Biochemistry
  • General Materials Science
  • Condensed Matter Physics

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