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==Pig Brain GABA-AT inactivated by (Z)-(1S,3S)-3-Amino-4-fluoromethylenyl-1-cyclopentanoic acid.==
==Pig Brain GABA-AT inactivated by (Z)-(1S,3S)-3-Amino-4-fluoromethylenyl-1-cyclopentanoic acid.==
<StructureSection load='4zsy' size='340' side='right' caption='[[4zsy]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
<StructureSection load='4zsy' size='340' side='right'caption='[[4zsy]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4zsy]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZSY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZSY FirstGlance]. <br>
<table><tr><td colspan='2'>[[4zsy]] 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=4ZSY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZSY FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 1.7&#8491;</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=4zsy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zsy RCSB], [http://www.ebi.ac.uk/pdbsum/4zsy PDBsum]</span></td></tr>
<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=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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zsy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsy OCA], [https://pdbe.org/4zsy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zsy RCSB], [https://www.ebi.ac.uk/pdbsum/4zsy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsy 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;">
== Publication Abstract from PubMed ==
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.
 
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>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==See Also==
</div>
*[[Aminotransferase 3D structures|Aminotransferase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Compton, P]]
[[Category: Large Structures]]
[[Category: Doud, E]]
[[Category: Sus scrofa]]
[[Category: Kelleher, N L]]
[[Category: Compton P]]
[[Category: Le, H V]]
[[Category: Doud E]]
[[Category: Lee, H]]
[[Category: Kelleher NL]]
[[Category: Liu, D]]
[[Category: Le HV]]
[[Category: Sanishvili, R]]
[[Category: Lee H]]
[[Category: Silverman, R B]]
[[Category: Liu D]]
[[Category: Wu, R]]
[[Category: Sanishvili R]]
[[Category: Amino-4-fluoromethylenyl-1-cyclopentanoic acid]]
[[Category: Silverman RB]]
[[Category: Gaba aminotransferase]]
[[Category: Wu R]]
[[Category: Inactivation]]
[[Category: Mechanism-based]]

Latest revision as of 15:16, 6 March 2024

Pig Brain GABA-AT inactivated by (Z)-(1S,3S)-3-Amino-4-fluoromethylenyl-1-cyclopentanoic acid.Pig Brain GABA-AT inactivated by (Z)-(1S,3S)-3-Amino-4-fluoromethylenyl-1-cyclopentanoic acid.

Structural highlights

4zsy is a 4 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.7Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

See Also

4zsy, resolution 1.70Å

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