Data di Pubblicazione:
2012
Citazione:
COMPUTATIONAL INVESTIGATION ON SUBSTRATE UPTAKE AND RELEASE IN A GLUTAMATE TRANSPORTER / G. Grazioso, V. Limongelli, D. Branduardi, E. Novellino, C. De Micheli, A. Cavalli, M. Parrinello. ((Intervento presentato al 6. convegno Nuove Prospettive in Chimica farmaceutica tenutosi a Riccione nel 2012.
Abstract:
An unbalance in the glutamate concentration along the neuronal network can
lead to an incorrect signal transduction and to severe neurodegenerative diseases
such as Alzheimer’s or Parkinson’s. Glutamate transporters play a crucial role in this
respect since they are responsible for the reuptake of the neurotransmitter from the
synaptic cleft thus controlling the glutamate concentration. Understanding the
molecular mechanism of this transporter can provide the possibility of an exogenous
control. Structural studies have shown that this transporter can assume four
conformations, thus suggesting a pronounced dynamical behavior. However, the last
state leading to the substrate internalization have not been characterized and many
aspects of the transporter mechanism still remain unclear.
Using metadynamics simulations, we investigate the substrate uptake from the
synaptic cleft and its release in the intracellular medium. In addition, we focus on the
role of ions and substrate during these processes and on the stability of the different
conformations assumed by the transporter.1 These dynamical results can complement
the available X-ray data and provide a thorough description of the entire process of
substrate uptake, internalization, and release.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Elenco autori:
G. Grazioso, V. Limongelli, D. Branduardi, E. Novellino, C. De Micheli, A. Cavalli, M. Parrinello
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