Crystal Structure of GABA-Aminotransferase, a Target for Antiepileptic Drug Therapy

γ-Aminobutyrate aminotransferase (GABA-AT), a pyridoxal phosphate-dependent enzyme, is responsible for the degradation of the inhibitory neurotransmitter GABA and is a target for antiepileptic drugs because its selective inhibition raises GABA concentrations in brain. The X-ray structure of pig GABA...

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Bibliographic Details
Published in:Biochemistry (Easton) 1999-07, Vol.38 (27), p.8628-8634
Main Authors: Storici, Paola, Capitani, Guido, De Biase, Daniela, Moser, Markus, John, Robert A, Jansonius, Johan N, Schirmer, Tilman
Format: Article
Language:English
Subjects:
4-Aminobutyrate Transaminase - chemistry
Amino Acid Sequence
Animals
Anticonvulsants - chemistry
Binding Sites
Computer Simulation
Crystallization
Crystallography, X-Ray
Epilepsy - drug therapy
Epilepsy - enzymology
gamma-Aminobutyric Acid - analogs & derivatives
gamma-Aminobutyric Acid - chemistry
gamma-Aminobutyric Acid - therapeutic use
Humans
Models, Molecular
Molecular Sequence Data
Protein Folding
Solutions
Swine
Vigabatrin
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Summary:γ-Aminobutyrate aminotransferase (GABA-AT), a pyridoxal phosphate-dependent enzyme, is responsible for the degradation of the inhibitory neurotransmitter GABA and is a target for antiepileptic drugs because its selective inhibition raises GABA concentrations in brain. The X-ray structure of pig GABA-AT has been determined to 3.0 Å resolution by molecular replacement with the distantly related enzyme ornithine aminotransferase. Both ω-aminotransferases have the same fold, but exhibit side chain replacements in the closely packed binding site that explain their respective specificities. The aldimines of GABA and the antiepileptic drug vinyl-GABA have been modeled into the active site.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi990478j