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| [[Image:1ohy.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1ohy| PDB=1ohy | SCENE= }} | | {{STRUCTURE_1ohy| PDB=1ohy | SCENE= }} |
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| '''4-AMINOBUTYRATE-AMINOTRANSFERASE INACTIVATED BY GAMMA-ETHYNYL GABA'''
| | ===4-AMINOBUTYRATE-AMINOTRANSFERASE INACTIVATED BY GAMMA-ETHYNYL GABA=== |
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| ==Overview==
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| Gamma-aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate-dependent enzyme responsible for the degradation of the inhibitory neurotransmitter GABA. GABA-AT is a validated target for antiepilepsy drugs because its selective inhibition raises GABA concentrations in brain. The antiepilepsy drug, gamma-vinyl-GABA (vigabatrin) has been investigated in the past by various biochemical methods and resulted in several proposals for its mechanisms of inactivation. In this study we solved and compared the crystal structures of pig liver GABA-AT in its native form (to 2.3-A resolution) and in complex with vigabatrin as well as with the close analogue gamma-ethynyl-GABA (to 2.3 and 2.8 A, respectively). Both inactivators form a covalent ternary adduct with the active site Lys-329 and the pyridoxal 5'-phosphate (PLP) cofactor. The crystal structures provide direct support for specific inactivation mechanisms proposed earlier on the basis of radio-labeling experiments. The reactivity of GABA-AT crystals with the two GABA analogues was also investigated by polarized absorption microspectrophotometry. The spectral data are discussed in relation to the proposed mechanism. Intriguingly, all three structures revealed a [2Fe-2S] cluster of yet unknown function at the center of the dimeric molecule in the vicinity of the PLP cofactors.
| | The line below this paragraph, {{ABSTRACT_PUBMED_14534310}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 14534310 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_14534310}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Transit peptide]] | | [[Category: Transit peptide]] |
| [[Category: Vigabatrin pyridoxal phosphate]] | | [[Category: Vigabatrin pyridoxal phosphate]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:52:04 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:28:45 2008'' |