1ohy

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[[Image:1ohy.jpg|left|200px]]<br /><applet load="1ohy" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1ohy.jpg|left|200px]]
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caption="1ohy, resolution 2.80&Aring;" />
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'''4-AMINOBUTYRATE-AMINOTRANSFERASE INACTIVATED BY GAMMA-ETHYNYL GABA'''<br />
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{{Structure
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|PDB= 1ohy |SIZE=350|CAPTION= <scene name='initialview01'>1ohy</scene>, resolution 2.80&Aring;
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|SITE= <scene name='pdbsite=AC1:S+Binding+Site+For+Chain+D'>AC1</scene>
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|LIGAND= <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> and <scene name='pdbligand=S:SULFUR ATOM'>S</scene>
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|ACTIVITY= [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]
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|GENE=
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}}
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'''4-AMINOBUTYRATE-AMINOTRANSFERASE INACTIVATED BY GAMMA-ETHYNYL GABA'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1OHY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=FE:'>FE</scene>, <scene name='pdbligand=PLP:'>PLP</scene> and <scene name='pdbligand=S:'>S</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:S+Binding+Site+For+Chain+D'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OHY OCA].
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1OHY is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OHY OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14534310 14534310]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/14534310 14534310]
[[Category: 4-aminobutyrate transaminase]]
[[Category: 4-aminobutyrate transaminase]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: vigabatrin pyridoxal phosphate]]
[[Category: vigabatrin pyridoxal phosphate]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:17:56 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:11:09 2008''

Revision as of 11:11, 20 March 2008

Image:1ohy.jpg


PDB ID 1ohy

Drag the structure with the mouse to rotate
, resolution 2.80Å
Sites:
Ligands: , and
Activity: 4-aminobutyrate transaminase, with EC number 2.6.1.19
Coordinates: save as pdb, mmCIF, xml



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

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