4y0d - Revision history

OCA at 13:02, 1 March 2024

OCA — Fri, 01 Mar 2024 13:02:16 GMT

←Older revision		Revision as of 13:02, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4y0d]] 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=4Y0D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y0D FirstGlance]. <br>		<table><tr><td colspan='2'>[[4y0d]] 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=4Y0D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y0D FirstGlance]. <br>
-	</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>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.19Å</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=4y0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0d OCA], [https://pdbe.org/4y0d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y0d RCSB], [https://www.ebi.ac.uk/pdbsum/4y0d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y0d ProSAT]</span></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=4y0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0d OCA], [https://pdbe.org/4y0d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y0d RCSB], [https://www.ebi.ac.uk/pdbsum/4y0d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y0d ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== 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.		[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 ==
-	gamma-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently, CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. This represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general.
-
-	Mechanism of Inactivation of gamma-Aminobutyric Acid Aminotransferase by (1S,3S)-3-Amino-4-difluoromethylene-1-cyclopentanoic Acid (CPP-115).,Lee H, Doud EH, Wu R, Sanishvili R, Juncosa JI, Liu D, Kelleher NL, Silverman RB J Am Chem Soc. 2015 Feb 10. PMID:25616005<ref>PMID:25616005</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4y0d" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Aminotransferase 3D structures\|Aminotransferase 3D structures]]		*[[Aminotransferase 3D structures\|Aminotransferase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 18:00, 26 April 2023

OCA — Wed, 26 Apr 2023 18:00:53 GMT

←Older revision		Revision as of 18:00, 26 April 2023
Line 1:		Line 1:

	==Gamma-aminobutyric acid aminotransferase inactivated by (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115)==		==Gamma-aminobutyric acid aminotransferase inactivated by (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115)==
-	<StructureSection load='4y0d' size='340' side='right' caption='[[4y0d]], [[Resolution\|resolution]] 2.19Å' scene=''>	+	<StructureSection load='4y0d' size='340' side='right'caption='[[4y0d]], [[Resolution\|resolution]] 2.19Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4y0d]] 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=4Y0D OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4Y0D FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4y0d]] 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=4Y0D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y0D FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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>~~	+	</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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y0h\|4y0h]]</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=4y0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0d OCA], [https://pdbe.org/4y0d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y0d RCSB], [https://www.ebi.ac.uk/pdbsum/4y0d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y0d ProSAT]</span></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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4y0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0d OCA], [~~http~~://pdbe.org/4y0d PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4y0d RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4y0d PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4y0d 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 4y0d" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4y0d" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aminotransferase 3D structures\|Aminotransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Pig~~]]	+	[[Category: Large Structures]]
-	[[Category: Dali, L]]	+	[[Category: Sus scrofa]]
-	[[Category: Emma~~, H D~~]]	+	[[Category: Dali L]]
-	[[Category: Hyunbeom, L]]	+	[[Category: Emma HD]]
-	[[Category: Jose~~, I J~~]]	+	[[Category: Hyunbeom L]]
-	[[Category: Neil, K]]	+	[[Category: Jose IJ]]
-	[[Category: Richard~~, B S~~]]	+	[[Category: Neil K]]
-	[[Category: Rui, W]]	+	[[Category: Richard BS]]
-	[[Category: Ruslan, S]]	+	[[Category: Rui W]]
-	~~[[Category: Gaba-at]]~~	+	[[Category: Ruslan S]]
-	~~[[Category: Inactivator]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 09:38, 22 November 2017

OCA — Wed, 22 Nov 2017 09:38:42 GMT

←Older revision		Revision as of 09:38, 22 November 2017
Line 3:		Line 3:
	<StructureSection load='4y0d' size='340' side='right' caption='[[4y0d]], [[Resolution\|resolution]] 2.19Å' scene=''>		<StructureSection load='4y0d' size='340' side='right' caption='[[4y0d]], [[Resolution\|resolution]] 2.19Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4y0d]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y0D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y0D FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4y0d]] 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=4Y0D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y0D FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y0h\|4y0h]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y0h\|4y0h]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4y0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0d OCA], [http://pdbe.org/4y0d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y0d RCSB], [http://www.ebi.ac.uk/pdbsum/4y0d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y0d 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=4y0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0d OCA], [http://pdbe.org/4y0d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y0d RCSB], [http://www.ebi.ac.uk/pdbsum/4y0d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y0d ProSAT]</span></td></tr>
	</table>		</table>
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4y0d" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4y0d" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Aminotransferase\|Aminotransferase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Pig]]
	[[Category: Dali, L]]		[[Category: Dali, L]]
	[[Category: Emma, H D]]		[[Category: Emma, H D]]

OCA at 01:49, 10 March 2017

OCA — Fri, 10 Mar 2017 01:49:27 GMT

←Older revision		Revision as of 01:49, 10 March 2017
Line 1:		Line 1:
		+
	==Gamma-aminobutyric acid aminotransferase inactivated by (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115)==		==Gamma-aminobutyric acid aminotransferase inactivated by (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115)==
	<StructureSection load='4y0d' size='340' side='right' caption='[[4y0d]], [[Resolution\|resolution]] 2.19Å' scene=''>		<StructureSection load='4y0d' size='340' side='right' caption='[[4y0d]], [[Resolution\|resolution]] 2.19Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y0h\|4y0h]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y0h\|4y0h]]</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=4y0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4y0d RCSB], [http://www.ebi.ac.uk/pdbsum/4y0d 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=4y0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0d OCA], [http://pdbe.org/4y0d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4y0d RCSB], [http://www.ebi.ac.uk/pdbsum/4y0d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4y0d ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	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 4y0d" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aminotransferase\|Aminotransferase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:50, 25 February 2015

OCA — Wed, 25 Feb 2015 13:50:59 GMT

←Older revision		Revision as of 13:50, 25 February 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Gamma-aminobutyric acid aminotransferase inactivated by (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115)==
		+	<StructureSection load='4y0d' size='340' side='right' caption='[[4y0d]], [[Resolution\|resolution]] 2.19Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4y0d]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y0D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y0D FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4y0h\|4y0h]]</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=4y0d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4y0d RCSB], [http://www.ebi.ac.uk/pdbsum/4y0d PDBsum]</span></td></tr>
		+	</table>
		+	== 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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	gamma-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently, CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. This represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general.

-	~~The entry 4y0d is ON HOLD~~	+	Mechanism of Inactivation of gamma-Aminobutyric Acid Aminotransferase by (1S,3S)-3-Amino-4-difluoromethylene-1-cyclopentanoic Acid (CPP-115).,Lee H, Doud EH, Wu R, Sanishvili R, Juncosa JI, Liu D, Kelleher NL, Silverman RB J Am Chem Soc. 2015 Feb 10. PMID:25616005<ref>PMID:25616005</ref>

-	~~Authors: Rui~~, W.~~, Ruslan,~~ S.~~, Hyunbeom, L~~., Emma, H.D., Jose, I.J~~., Neil, K., Richard, B.S., Dali, L.~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Gamma-aminobutyric acid aminotransferase inactivated by (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115)~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: Richard, B.S]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Dali, L]]
		+	[[Category: Emma, H D]]
		+	[[Category: Hyunbeom, L]]
		+	[[Category: Jose, I J]]
		+	[[Category: Neil, K]]
		+	[[Category: Richard, B S]]
	[[Category: Rui, W]]		[[Category: Rui, W]]
-	[[Category: Emma, H.D]]
-	[[Category: Neil, K]]
	[[Category: Ruslan, S]]		[[Category: Ruslan, S]]
-	[[Category: ~~Jose, I.J~~]]	+	[[Category: Gaba-at]]
-	[[Category: ~~Hyunbeom, L~~]]	+	[[Category: Inactivator]]
-	[[Category: ~~Dali, L~~]]	+	[[Category: Transferase]]

OCA at 11:51, 18 February 2015

OCA — Wed, 18 Feb 2015 11:51:14 GMT

←Older revision		Revision as of 11:51, 18 February 2015
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	The entry 4y0d is ON HOLD		The entry 4y0d is ON HOLD

-	Authors: Rui W., Ruslan S., Hyunbeom L., Emma H. D., Jose I. J., Neil K., Richard B. S., Dali L.	+	Authors: Rui, W., Ruslan, S., Hyunbeom, L., Emma, H.D., Jose, I.J., Neil, K., Richard, B.S., Dali, L.

	Description: Gamma-aminobutyric acid aminotransferase inactivated by (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115)		Description: Gamma-aminobutyric acid aminotransferase inactivated by (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115)
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Richard B. S]]	+	[[Category: Richard, B.S]]
-	[[Category: ~~Jose I. J~~]]	+	[[Category: Rui, W]]
-	[[Category: ~~Hyunbeom L~~]]	+	[[Category: Emma, H.D]]
-	[[Category: ~~Ruslan S~~]]	+	[[Category: Neil, K]]
-	[[Category: ~~Neil K~~]]	+	[[Category: Ruslan, S]]
-	[[Category: ~~Emma H~~. D]]	+	[[Category: Jose, I.J]]
-	[[Category: ~~Dali~~ L]]	+	[[Category: Hyunbeom, L]]
-	[[Category: ~~Rui W~~]]	+	[[Category: Dali, L]]

OCA: Protected "4y0d" [edit=sysop:move=sysop]

OCA — Thu, 12 Feb 2015 10:57:04 GMT

Protected "4y0d" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:57, 12 February 2015

OCA: New page: '''Unreleased structure''' The entry 4y0d is ON HOLD Authors: Rui W., Ruslan S., Hyunbeom L., Emma H. D., Jose I. J., Neil K., Richard B. S., Dali L. Description: Gamma-aminobutyric ac...

OCA — Thu, 12 Feb 2015 10:57:02 GMT

New page: '''Unreleased structure''' The entry 4y0d is ON HOLD Authors: Rui W., Ruslan S., Hyunbeom L., Emma H. D., Jose I. J., Neil K., Richard B. S., Dali L. Description: Gamma-aminobutyric ac...

New page

'''Unreleased structure'''

The entry 4y0d is ON HOLD

Authors: Rui W., Ruslan S., Hyunbeom L., Emma H. D., Jose I. J., Neil K., Richard B. S., Dali L.

Description: Gamma-aminobutyric acid aminotransferase inactivated by (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (CPP-115)
[[Category: Unreleased Structures]]
[[Category: Richard B. S]]
[[Category: Jose I. J]]
[[Category: Hyunbeom L]]
[[Category: Ruslan S]]
[[Category: Neil K]]
[[Category: Emma H. D]]
[[Category: Dali L]]
[[Category: Rui W]]