| Major human gamma-aminobutyrate transporter: in silico prediction of substrate efficacy. | |
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MedLine Citation:
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PMID: 17967412 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The inhibitory gamma-aminobutyric acid transporter subtype 1 (GAT1) maintains low resting synaptic GABA level, and is a potential target for antiepileptic drugs. Here we report a high scored binding mode that associates GABA with gating in a homology model of the human GAT1. Docking and molecular dynamics calculations recognize the amino function of GABA in the H-bonding state favoring TM1 and TM8 helix residues Y60 and S396, respectively. This ligand binding mode visibly ensures the passage of GABA and substrate inhibitors (R)-homo-beta-Pro, (R)-nipecotic acid, and guvacine. It might therefore represent the principle, sufficient for sorting out less-effective or non-GAT ligands such as beta-Pro, (S)-nipecotic acid, (R)-baclofen, Glu, and Leu. |
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Authors:
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Anna Palló; Akos Bencsura; László Héja; Tamás Beke; András Perczel; Julianna Kardos; Agnes Simon |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-10-29 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 364 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-11-20 Completed Date: 2007-12-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 952-8 Citation Subset: IM |
Affiliation:
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Department of Neurochemistry, Chemical Research Center, Hungarian Academy of Sciences, H-1025 Pusztaszeri út 59-67, Budapest, Hungary. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Binding Sites Computer Simulation GABA Plasma Membrane Transport Proteins / chemistry*, ultrastructure* Humans Models, Chemical* Models, Molecular* Protein Binding Protein Conformation Substrate Specificity gamma-Aminobutyric Acid / chemistry* |
| Chemical | |
Reg. No./Substance:
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0/GABA Plasma Membrane Transport Proteins; 0/SLC6A1 protein, human; 56-12-2/gamma-Aminobutyric Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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