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- W3029570638 endingPage "3083" @default.
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- W3029570638 abstract "Glutamate receptors are essential ligand-gated ion channels in the central nervous system that mediate excitatory synaptic transmission in response to the release of glutamate from presynaptic terminals. The structural and biophysical basis underlying the function of these receptors has been studied for decades by a wide range of approaches. However recent structural, pharmacological and genetic studies have provided new insight into the regions of this protein that are critical determinants of receptor function. Lack of variation in specific areas of the protein amino acid sequences in the human population has defined three regions in each receptor subunit that are under selective pressure, which has focused research efforts and driven new hypotheses. In addition, these three closely positioned elements reside near a cavity that is shown by multiple studies to be a likely site of action for allosteric modulators, one of which is currently in use as an FDA-approved anticonvulsant. These structural elements are capable of controlling gating of the pore, and appear to permit some modulators bound within the cavity to also alter permeation properties. This creates a new precedent whereby features of the channel pore can be modulated by exogenous drugs that bind outside the pore. The convergence of structural, genetic, biophysical and pharmacological approaches is a powerful means to gain insight into the complex biological processes defined by neurotransmitter receptor function." @default.
- W3029570638 created "2020-06-05" @default.
- W3029570638 creator A5004177357 @default.
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- W3029570638 date "2020-06-15" @default.
- W3029570638 modified "2023-10-18" @default.
- W3029570638 title "Hodgkin–Huxley–Katz Prize Lecture: Genetic and pharmacological control of glutamate receptor channel through a highly conserved gating motif" @default.
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