title: Molecular mechanism of ATP hydrolysis in F1-ATPase revealed by molecular simulations and single-molecule observations.
abstract: 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 F(1)-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(γ)-O(β) 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.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Japan. hayashig@kuchem.kyoto-u.ac.jp
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Hayashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueno
authors.forename: Abdul Rajjak
authors.initials: AR
authors.lastname: Shaikh
authors.forename: Myco
authors.initials: M
authors.lastname: Umemura
authors.forename: Motoshi
authors.initials: M
authors.lastname: Kamiya
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ito
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Ikeguchi
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Komoriya
authors.forename: Ryota
authors.initials: R
authors.lastname: Iino
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Noji
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D006868:Hydrolysis; D056004:Molecular Dynamics Simulation; D009154:Mutation; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases