Conformational change of adenosine deaminase during ligand-exchange in a crystal.
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.
Graduate School of Science, Osaka Prefecture University, Gakuencho 1-1, Sakai, Osaka 599-8531, Japan. kinotk@b.s.osakafu-u.ac.jp
Takayoshi
T
Kinoshita
Toshiji
T
Tada
Isao
I
Nakanishi
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D000243:Adenosine Deaminase / Q000737:chemistry*; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry*; D008024:Ligands; D011487:Protein Conformation; D014372:Tubercidin / Q000737:chemistry; D014867:Water / Q000737:chemistry
D004791:Enzyme Inhibitors; D008024:Ligands; D014867:Water; C048086:1-deazaadenosine; C010192:9-(2-hydroxy-3-nonyl)adenine; D000243:Adenosine Deaminase; D000225:Adenine; D014372:Tubercidin