Structural Basis of Compound Recognition by Adenosine Deaminase

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• 作者：Takayoshi Kinoshita ; Isao Nakanishi ; Tadashi Terasaka ; Masako Kuno ; Nobuo Seki ; Masaichi Warizaya ; Hiroyoshi Matsumura ; Tsuyoshi Inoue ; Kazuhumi Takano ; Hiroaki Adachi ; Yusuke Mori ; and Takashi Fujii
• 刊名：Biochemistry
• 出版年：2005
• 出版时间：August 9, 2005
• 年：2005
• 卷：44
• 期：31
• 页码：10562 - 10569
• 全文大小：519K
• 年卷期：v.44,no.31(August 9, 2005)
• ISSN：1520-4995

文摘

Structural snapshots corresponding to various states enable elucidation of the molecularrecognition mechanism of enzymes. Adenosine deaminase has two distinct conformations, an open formand a closed form, although it has so far been unclear what factors influence adaptation of the alternativeconformations. Herein, we have determined the first nonligated structure as an initial state, which was theopen form, and have thereby rationally deduced the molecular recognition mechanism. Inspection of theactive site in the nonligated and ligated states indicated that occupancy at one of the water-binding positionsin the nonligated state was highly significant in determining alternate conformations. When this positionis 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 shouldgreatly assist structure-oriented drug design and enable control of the enzymatic activity.