4zsw: Difference between revisions
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</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='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> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zsy|4zsy]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zsy|4zsy]]</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://www.rcsb.org/pdb/explore.do?structureId=4zsw RCSB], [http://www.ebi.ac.uk/pdbsum/4zsw PDBsum]</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]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4zsw" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Inactivation]] | [[Category: Inactivation]] | ||
[[Category: Mechanism-based]] | [[Category: Mechanism-based]] | ||
[[Category: Transferase-transferase inhibitor complex]] | |||
Revision as of 10:50, 30 September 2015
Pig Brain GABA-AT inactivated by (E)-(1S,3S)-3-Amino-4-fluoromethylenyl-1-cyclopentanoic acidPig Brain GABA-AT inactivated by (E)-(1S,3S)-3-Amino-4-fluoromethylenyl-1-cyclopentanoic acid
Structural highlights
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. Publication Abstract from PubMedWhen 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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