Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor

J Med Chem. 2010 Jul 22;53(14):5352-5. doi: 10.1021/jm100249w.

Abstract

We report two crystal structures of the PARP domain of human tankyrase-2 (TNKS2). Tankyrases are involved in fundamental cellular processes such as telomere homeostasis and Wnt signaling. The complex of TNKS2 with the potent inhibitor XAV939 provides insights into the molecular basis of the strong interaction and suggests routes for further development of tankyrase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Heterocyclic Compounds, 3-Ring / chemistry*
  • Humans
  • Models, Molecular
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Signal Transduction
  • Tankyrases / antagonists & inhibitors
  • Tankyrases / chemistry*
  • Wnt Proteins / physiology*

Substances

  • Heterocyclic Compounds, 3-Ring
  • Recombinant Proteins
  • Wnt Proteins
  • XAV939
  • TNKS2 protein, human
  • Tankyrases

Associated data

  • PDB/3KR7
  • PDB/3KR8