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| [[Image:1ohy.jpg|left|200px]]
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| {{Structure
| | ==4-AMINOBUTYRATE-AMINOTRANSFERASE inactivated by gamma-ethynyl GABA== |
| |PDB= 1ohy |SIZE=350|CAPTION= <scene name='initialview01'>1ohy</scene>, resolution 2.80Å
| | <StructureSection load='1ohy' size='340' side='right'caption='[[1ohy]], [[Resolution|resolution]] 2.80Å' scene=''> |
| |SITE= <scene name='pdbsite=AC1:S+Binding+Site+For+Chain+D'>AC1</scene> | | == Structural highlights == |
| |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>
| | <table><tr><td colspan='2'>[[1ohy]] is a 4 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OHY FirstGlance]. <br> |
| |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]
| | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| |GENE=
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=GEG:(4E)-4-AMINOHEX-4-ENOIC+ACID'>GEG</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene></td></tr> |
| }}
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ohy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ohy OCA], [https://pdbe.org/1ohy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ohy RCSB], [https://www.ebi.ac.uk/pdbsum/1ohy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ohy ProSAT]</span></td></tr> |
| | | </table> |
| '''4-AMINOBUTYRATE-AMINOTRANSFERASE INACTIVATED BY GAMMA-ETHYNYL GABA'''
| | == Function == |
| | | [https://www.uniprot.org/uniprot/GABT_PIG GABT_PIG] Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine. |
| | | == Evolutionary Conservation == |
| ==Overview== | | [[Image:Consurf_key_small.gif|200px|right]] |
| 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.
| | Check<jmol> |
| | | <jmolCheckbox> |
| ==About this Structure== | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oh/1ohy_consurf.spt"</scriptWhenChecked> |
| 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].
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | | <text>to colour the structure by Evolutionary Conservation</text> |
| ==Reference==
| | </jmolCheckbox> |
| 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]
| | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ohy ConSurf]. |
| [[Category: 4-aminobutyrate transaminase]]
| | <div style="clear:both"></div> |
| [[Category: Single protein]] | | __TOC__ |
| | </StructureSection> |
| | [[Category: Large Structures]] |
| [[Category: Sus scrofa]] | | [[Category: Sus scrofa]] |
| [[Category: Schirmer, T.]] | | [[Category: Schirmer T]] |
| [[Category: Storici, P.]] | | [[Category: Storici P]] |
| [[Category: FE]]
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| [[Category: PLP]]
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| [[Category: S]]
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| [[Category: 4-aminobutyric acid]]
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| [[Category: aminotransferase]]
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| [[Category: antiepileptic drug target]]
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| [[Category: mitochondrion]]
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| [[Category: neurotransmitter degradation]]
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| [[Category: plp-dependent enzyme]]
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| [[Category: transferase]]
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| [[Category: transit peptide]]
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| [[Category: vigabatrin pyridoxal phosphate]]
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| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 13:04:10 2008''
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