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Publication Abstract from PubMed

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.

Conformational change of adenosine deaminase during ligand-exchange in a crystal.,Kinoshita T, Tada T, Nakanishi I Biochem Biophys Res Commun. 2008 Aug 15;373(1):53-7. Epub 2008 Jun 10. PMID:18549808^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.