1ohy

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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'''
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===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.
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(as it appears on PubMed at http://www.pubmed.gov), where 14534310 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14534310}}
==About this Structure==
==About this Structure==
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[[Category: Transit peptide]]
[[Category: Transit peptide]]
[[Category: Vigabatrin pyridoxal phosphate]]
[[Category: Vigabatrin pyridoxal phosphate]]
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Revision as of 11:28, 29 July 2008

Image:1ohy.png

Template:STRUCTURE 1ohy

4-AMINOBUTYRATE-AMINOTRANSFERASE INACTIVATED BY GAMMA-ETHYNYL GABA

Template:ABSTRACT PUBMED 14534310

About this Structure

1OHY is a Single protein structure of sequence from Sus scrofa. Full crystallographic information is available from OCA.

Reference

Structures of gamma-aminobutyric acid (GABA) aminotransferase, a pyridoxal 5'-phosphate, and [2Fe-2S] cluster-containing enzyme, complexed with gamma-ethynyl-GABA and with the antiepilepsy drug vigabatrin., Storici P, De Biase D, Bossa F, Bruno S, Mozzarelli A, Peneff C, Silverman RB, Schirmer T, J Biol Chem. 2004 Jan 2;279(1):363-73. Epub 2003 Oct 8. PMID:14534310

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