Crystal structure of GABA-aminotransferase, a target for antiepileptic drug therapy.
gamma-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 A resolution by molecular replacement with the distantly related enzyme ornithine aminotransferase. Both omega-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.
Division of Structural Biology, Biozentrum, University of Basel, Switzerland. storici@ubaclu.unibas.ch
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P
Storici
G
G
Capitani
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De Biase
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M
Moser
R A
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John
J N
JN
Jansonius
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T
Schirmer
D000612:4-Aminobutyrate Transaminase / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D003460:Crystallization; D018360:Crystallography, X-Ray; D004827:Epilepsy / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D012996:Solutions; D013552:Swine; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use
D000927:Anticonvulsants; D012996:Solutions; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin