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| <StructureSection load='4zsw' size='340' side='right'caption='[[4zsw]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='4zsw' size='340' side='right'caption='[[4zsw]], [[Resolution|resolution]] 1.70Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[4zsw]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Pig Pig]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZSW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZSW FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4zsw]] 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=4ZSW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZSW FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FSF:4FE-2S-O+HYBRID+CLUSTER'>FSF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RW2:(1S)-4-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]CYCLOPENT-3-ENE-1,3-DICARBOXYLIC+ACID'>RW2</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zsy|4zsy]]</td></tr>
| | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=RW2:(1S)-4-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]CYCLOPENT-3-ENE-1,3-DICARBOXYLIC+ACID'>RW2</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ABAT, GABAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 PIG])</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=4zsw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsw OCA], [https://pdbe.org/4zsw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zsw RCSB], [https://www.ebi.ac.uk/pdbsum/4zsw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsw ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zsw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsw OCA], [http://pdbe.org/4zsw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zsw RCSB], [http://www.ebi.ac.uk/pdbsum/4zsw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsw ProSAT]</span></td></tr> | |
| </table> | | </table> |
| == Function == | | == Function == |
| [[http://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. | | [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. |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| When gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian central nervous system, falls below a threshold level, seizures occur. One approach to raise GABA concentrations is to inhibit GABA aminotransferase (GABA-AT), a pyridoxal 5'-phosphate-dependent enzyme that degrades GABA. We have previously developed (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115), which is 186 times more efficient in inactivating GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. We also developed (E)- and (Z)-(1S,3S)-3-amino-4-fluoromethylenyl-1-cyclopentanoic acid (1 and 2, respectively), monofluorinated analogs of CPP-115, which are comparable to vigabatrin in inactivating GABA-AT. Here, we report the mechanism of inactivation of GABA-AT by 1 and 2. Both produce a metabolite that induces disruption of the Glu270-Arg445 salt bridge to accommodate interaction between the metabolite formyl group and Arg445. This is the second time that Arg445 has interacted with a ligand and is involved in GABA-AT inactivation, thereby confirming the importance of Arg445 in future inactivator design.
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| Mechanism of Inactivation of GABA Aminotransferase by (E)- and (Z)-(1S,3S)-3-Amino-4-fluoromethylenyl-1-cyclopentanoic Acid.,Lee H, Le HV, Wu R, Doud E, Sanishvili R, Kellie JF, Compton PD, Pachaiyappan B, Liu D, Kelleher NL, Silverman RB ACS Chem Biol. 2015 Jul 6. PMID:26110556<ref>PMID:26110556</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 4zsw" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Aminotransferase 3D structures|Aminotransferase 3D structures]] | | *[[Aminotransferase 3D structures|Aminotransferase 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Pig]] | | [[Category: Sus scrofa]] |
| [[Category: Compton, P]] | | [[Category: Compton P]] |
| [[Category: Doud, E]] | | [[Category: Doud E]] |
| [[Category: Kelleher, N L]] | | [[Category: Kelleher NL]] |
| [[Category: Le, H V]] | | [[Category: Le HV]] |
| [[Category: Lee, H]] | | [[Category: Lee H]] |
| [[Category: Liu, D]] | | [[Category: Liu D]] |
| [[Category: Sanishvili, R]] | | [[Category: Sanishvili R]] |
| [[Category: Silverman, R B]] | | [[Category: Silverman RB]] |
| [[Category: Wu, R]] | | [[Category: Wu R]] |
| [[Category: Amino-4-fluoromethylenyl-1-cyclopentanoic acid]]
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| [[Category: Gaba aminotransferase]]
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| [[Category: Inactivation]]
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| [[Category: Mechanism-based]]
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| [[Category: Transferase-transferase inhibitor complex]]
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