4zsy: Difference between revisions

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== 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.

== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

==See Also==

*[[Aminotransferase 3D structures|Aminotransferase 3D structures]]

== References ==

__TOC__

</StructureSection>

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@@ Line 10: / Line 10: @@
 == 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.
+<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>
+</div>
+<div class="pdbe-citations 4zsy" style="background-color:#fffaf0;"></div>
 ==See Also==
 *[[Aminotransferase 3D structures|Aminotransferase 3D structures]]
+== References ==
+<references/>
 __TOC__
 </StructureSection>