1ohy

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[[Image:1ohy.jpg|left|200px]]
[[Image:1ohy.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 1ohy |SIZE=350|CAPTION= <scene name='initialview01'>1ohy</scene>, resolution 2.80&Aring;
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The line below this paragraph, containing "STRUCTURE_1ohy", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:S+Binding+Site+For+Chain+D'>AC1</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=GEG:(4E)-4-AMINOHEX-4-ENOIC+ACID'>GEG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5&#39;-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=S:SULFUR+ATOM'>S</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/4-aminobutyrate_transaminase 4-aminobutyrate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.19 2.6.1.19] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_1ohy| PDB=1ohy | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ohy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ohy OCA], [http://www.ebi.ac.uk/pdbsum/1ohy PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ohy RCSB]</span>
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}}
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'''4-AMINOBUTYRATE-AMINOTRANSFERASE INACTIVATED BY GAMMA-ETHYNYL GABA'''
'''4-AMINOBUTYRATE-AMINOTRANSFERASE INACTIVATED BY GAMMA-ETHYNYL GABA'''
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[[Category: Storici, P.]]
[[Category: Storici, P.]]
[[Category: 4-aminobutyric acid]]
[[Category: 4-aminobutyric acid]]
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[[Category: aminotransferase]]
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[[Category: Aminotransferase]]
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[[Category: antiepileptic drug target]]
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[[Category: Antiepileptic drug target]]
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[[Category: mitochondrion]]
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[[Category: Mitochondrion]]
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[[Category: neurotransmitter degradation]]
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[[Category: Neurotransmitter degradation]]
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[[Category: plp-dependent enzyme]]
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[[Category: Plp-dependent enzyme]]
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[[Category: transferase]]
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[[Category: Transferase]]
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[[Category: transit peptide]]
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[[Category: Transit peptide]]
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[[Category: vigabatrin pyridoxal phosphate]]
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[[Category: Vigabatrin pyridoxal phosphate]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:52:04 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:45:36 2008''
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Revision as of 00:52, 3 May 2008

Image:1ohy.jpg

Template:STRUCTURE 1ohy

4-AMINOBUTYRATE-AMINOTRANSFERASE INACTIVATED BY GAMMA-ETHYNYL GABA


Overview

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.

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 Page seeded by OCA on Sat May 3 03:52:04 2008

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