Sekikaic acid and lobaric acid target a dynamic interface of the coactivator CBP/p300

Angew Chem Int Ed Engl. 2012 Nov 5;51(45):11258-62. doi: 10.1002/anie.201206815. Epub 2012 Oct 8.

Abstract

Capturing a coactivator, naturally: the natural products sekikaic acid and lobaric acid, isolated after a high-throughput screen of a structurally diverse extract collection, effectively target the dynamic binding interfaces of the GACKIX domain of the coactivator CBP/p300. These molecules are the most effective inhibitors of the GACKIX domain yet described and are uniquely selective for this domain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Depsides / chemistry*
  • Depsides / metabolism
  • Lactones / chemistry*
  • Lactones / metabolism
  • Models, Molecular
  • Molecular Dynamics Simulation
  • Protein Structure, Tertiary
  • Salicylates / chemistry*
  • Salicylates / metabolism
  • p300-CBP Transcription Factors / antagonists & inhibitors
  • p300-CBP Transcription Factors / chemistry*
  • p300-CBP Transcription Factors / genetics
  • p300-CBP Transcription Factors / metabolism

Substances

  • Depsides
  • Lactones
  • Salicylates
  • lobaric acid
  • p300-CBP Transcription Factors