Structural Basis of Compound Recognition by Adenosine Deaminase
| Autor: | Hiroaki Adachi, Masako Kuno, Isao Nakanishi, Nobuo Seki, Yusuke Mori, Takashi Fujii, K. Takano, Masaichi Warizaya, Hiroyoshi Matsumura, Tsuyoshi Inoue, Tadashi Terasaka, Takayoshi Kinoshita |
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| Rok vydání: | 2005 |
| Předmět: |
Binding Sites
biology Basis (linear algebra) Adenosine Deaminase Protein Conformation Chemistry Stereochemistry Water Active site Crystallography X-Ray Ligands Biochemistry Structure-Activity Relationship Molecular recognition Adenosine deaminase Hydrolase Adenosine Deaminase Inhibitors biology.protein Animals Humans Cattle Open form Enzyme Inhibitors |
| Zdroj: | Biochemistry. 44:10562-10569 |
| ISSN: | 1520-4995 0006-2960 |
| Popis: | Structural snapshots corresponding to various states enable elucidation of the molecular recognition mechanism of enzymes. Adenosine deaminase has two distinct conformations, an open form and a closed form, although it has so far been unclear what factors influence adaptation of the alternative conformations. Herein, we have determined the first nonligated structure as an initial state, which was the open form, and have thereby rationally deduced the molecular recognition mechanism. Inspection of the active site in the nonligated and ligated states indicated that occupancy at one of the water-binding positions in the nonligated state was highly significant in determining alternate conformations. When this position is empty, subsequent movement of Phe65 toward the space induces the closed form. On the other hand, while occupied, the overall conformation remains in the open form. This structural understanding should greatly assist structure-oriented drug design and enable control of the enzymatic activity. |
| Databáze: | OpenAIRE |
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