Structure-based repurposing of FDA-approved drugs as inhibitors of NEDD8-activating enzyme

Hai-Jing Zhong, Li-Juan Liu, Daniel Shiu-Hin Chan, Hui-Min David Wang, Philip Wai Hong Chan, Dik-Lung Edmond Ma, Chung-Hang Duncan Leung

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

We report the discovery of an inhibitor of NEDD8-activating enzyme (NAE) by an integrated virtual screening approach. Piperacillin 1 inhibited NAE activity in cell-free and cell-based systems with high selectivity. Furthermore, piperacillin 1 was able to inhibit the degradation of the NAE downstream protein substrate p27kip1. Our molecular modeling and kinetic studies suggested that this compound may act as a non-covalent ATP-competitive inhibitor of NAE
Original languageEnglish
Pages (from-to)211 - 215
Number of pages5
JournalBiochimie
Volume102
Issue number1
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Ubiquitin-Protein Ligases
  • ligases CRLs
  • Cullin Proteins

Cite this