Download MendeleyConformational change of adenosine deaminase during ligand-exchange in a crystal
Kinoshita, T., Tada, T., Nakanishi, I.(2008) Biochem Biophys Res Commun 373: 53-57
- PubMed: 18549808
- DOI: https://doi.org/10.1016/j.bbrc.2008.05.180
- Primary Citation of Related Structures:
2Z7G - PubMed Abstract:
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.
Organizational Affiliation:
Graduate School of Science, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan. kinotk@b.s.osakafu-u.ac.jp
