Conformational change of adenosine deaminase during ligand-exchange in a crystal

Biochem Biophys Res Commun. 2008 Aug 15;373(1):53-7. doi: 10.1016/j.bbrc.2008.05.180. Epub 2008 Jun 10.


Adenosine deaminase (ADA) perpetuates chronic inflammation by degrading extracellular adenosine which is toxic for lymphocytes. ADA has two distinct conformations: open form and closed form. From the crystal structures with various ligands, the non-nucleoside type inhibitors bind to the active site occupying the critical water-binding-position and sustain the open form of apo-ADA. In contrast, substrate mimics do not occupy the critical position, and induce the large conformational change to the closed form. However, it is difficult to predict the binding of (+)-erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), as it possesses characteristic parts of both the substrate and the non-nucleoside inhibitors. The crystal structure shows that EHNA binds to the open form through a novel recognition of the adenine base accompanying conformational change from the closed form of the PR-ADA complex in crystalline state.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / chemistry
  • Adenosine Deaminase / chemistry*
  • Animals
  • Binding Sites
  • Cattle
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemistry*
  • Ligands
  • Protein Conformation
  • Tubercidin / chemistry
  • Water / chemistry


  • Enzyme Inhibitors
  • Ligands
  • Water
  • 1-deazaadenosine
  • 9-(2-hydroxy-3-nonyl)adenine
  • Adenosine Deaminase
  • Adenine
  • Tubercidin