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Mechanism of inhibition of the V-type molecular motor by tributyltin chloride.

ABSTRACT: Tributyltin chloride (TBT-Cl) is an endocrine disruptor found in many animal species, and it is also known to be an inhibitor for the V-ATPases that are emerging as potential targets in the treatment of diseases such as osteoporosis and cancer. We demonstrated by using biochemical and single-molecular imaging techniques that TBT-Cl arrests an elementary step for rotary catalysis of the V(1) motor domain. In the presence of TBT-Cl, the consecutive rotation of V(1) paused for a long duration ( approximately 0.5 s), even at saturated ATP concentrations, and the pausing positions were localized at 120 degrees intervals. Analysis of both the pausing time and moving time revealed that TBT-Cl has little effect on the binding affinity for ATP, but, rather, it arrests the catalytic event(s). This is the first report to demonstrate that an inhibitor arrests an elementary step for rotary catalysis of a V-type ATP-driven rotary motor.

SUBMITTER: Takeda M

PROVIDER: S-EPMC2716569 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Mechanism of inhibition of the V-type molecular motor by tributyltin chloride.

Takeda Mizuho M Suno-Ikeda Chiyo C Shimabukuro Katsuya K Yoshida Masasuke M Yokoyama Ken K

Biophysical journal 20090201 3

Tributyltin chloride (TBT-Cl) is an endocrine disruptor found in many animal species, and it is also known to be an inhibitor for the V-ATPases that are emerging as potential targets in the treatment of diseases such as osteoporosis and cancer. We demonstrated by using biochemical and single-molecular imaging techniques that TBT-Cl arrests an elementary step for rotary catalysis of the V(1) motor domain. In the presence of TBT-Cl, the consecutive rotation of V(1) paused for a long duration ( app ...[more]

PMID: 19186155

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