Molecular Mechanism of ATP Hydrolysis in F1-ATPase Revealed by Molecular Simulations and Single-Molecule Observations

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• 作者：Shigehiko Hayashi ; Hiroshi Ueno ; Abdul Rajjak Shaikh ; Myco Umemura ; Motoshi Kamiya ; Yuko Ito ; Mitsunori Ikeguchi ; Yoshihito Komoriya ; Ryota Iino ; Hiroyuki Noji
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：May 23, 2012
• 年：2012
• 卷：134
• 期：20
• 页码：8447-8454
• 全文大小：398K
• 年卷期：v.134,no.20(May 23, 2012)
• ISSN：1520-5126

文摘

Enzymatic hydrolysis of nucleotide triphosphate (NTP) plays a pivotal role in protein functions. In spite of its biological significance, however, the chemistry of the hydrolysis catalysis remains obscure because of the complex nature of the reaction. Here we report a study of the molecular mechanism of hydrolysis of adenosine triphosphate (ATP) in F₁-ATPase, an ATP-driven rotary motor protein. Molecular simulations predicted and single-molecule observation experiments verified that the rate-determining step (RDS) is proton transfer (PT) from the lytic water molecule, which is strongly activated by a metaphosphate generated by a preceding P_纬鈥揙_尾 bond dissociation (POD). Catalysis of the POD that triggers the chain activation of the PT is fulfilled by hydrogen bonds between Walker motif A and an arginine finger, which commonly exist in many NTPases. The reaction mechanism unveiled here indicates that the protein can regulate the enzymatic activity for the function in both the POD and PT steps despite the fact that the RDS is the PT step.