Mechanism of inhibition of the V-type molecular motor by tributyltin chloride.
Biophys J
; 96(3): 1210-7, 2009 Feb.
Article
em En
| MEDLINE
| ID: mdl-19186155
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos de Trialquitina
/
Thermus thermophilus
/
ATPases Vacuolares Próton-Translocadoras
/
Disruptores Endócrinos
Idioma:
En
Revista:
Biophys J
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão