5vwq - Revision history

OCA at 14:32, 29 November 2023

OCA — Wed, 29 Nov 2023 14:32:37 GMT

←Older revision		Revision as of 14:32, 29 November 2023
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	==E.coli Aspartate aminotransferase-(1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid (FCP)==		==E.coli Aspartate aminotransferase-(1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid (FCP)==
-	<StructureSection load='5vwq' size='340' side='right' caption='[[5vwq]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='5vwq' size='340' side='right'caption='[[5vwq]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vwq]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Ecoli Ecoli~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VWQ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5VWQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vwq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VWQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VWQ FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name='pdbligand=PMP:4-DEOXY-4-AMINOPYRIDOXAL-5-PHOSPHATE'>PMP</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]] 1.8Å</td></tr>
-	~~<tr~~ id~~='related'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Related_structure~~\|~~Related:]]</b></td><td class="sblockDat">[[5vwo\|5vwo~~]]</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PMP:4-DEOXY-4-AMINOPYRIDOXAL-5-PHOSPHATE'>PMP</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>aspC, b0928, JW0911 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~83333 ECOLI])</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=5vwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vwq OCA], [https://pdbe.org/5vwq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vwq RCSB], [https://www.ebi.ac.uk/pdbsum/5vwq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vwq ProSAT]</span></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[http://en.wikipedia.org/wiki/Aspartate_transaminase Aspartate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.1 2.6.1.1]~~ </~~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=5vwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vwq OCA], [~~http~~://pdbe.org/5vwq PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5vwq RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5vwq PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5vwq ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/AAT_ECOLI AAT_ECOLI]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 5vwq" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5vwq" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aspartate aminotransferase 3D structures\|Aspartate aminotransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Aspartate transaminase~~]]	+	[[Category: Escherichia coli K-12]]
-	[[Category: ~~Ecoli~~]]	+	[[Category: Large Structures]]
-	[[Category: Lehrer, H]]	+	[[Category: Lehrer H]]
-	[[Category: Liu, D]]	+	[[Category: Liu D]]
-	[[Category: Mascarenhas, R]]	+	[[Category: Mascarenhas R]]
-	[[Category: Ringe, D]]	+	[[Category: Ringe D]]
-	~~[[Category: 3]]~~	+
-	~~[[Category: Aspartate aminotransferase]]~~	+
-	~~[[Category: Mechanism-based inactivator]]~~	+
-	~~[[Category: Pmp]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 20:09, 15 November 2017

OCA — Wed, 15 Nov 2017 20:09:32 GMT

←Older revision		Revision as of 20:09, 15 November 2017
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	<StructureSection load='5vwq' size='340' side='right' caption='[[5vwq]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='5vwq' size='340' side='right' caption='[[5vwq]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5vwq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VWQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5vwq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VWQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PMP:4-DEOXY-4-AMINOPYRIDOXAL-5-PHOSPHATE'>PMP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PMP:4-DEOXY-4-AMINOPYRIDOXAL-5-PHOSPHATE'>PMP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vwo\|5vwo]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5vwo\|5vwo]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">aspC, b0928, JW0911 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aspartate_transaminase Aspartate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.1 2.6.1.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aspartate_transaminase Aspartate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.1 2.6.1.1] </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=5vwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vwq OCA], [http://pdbe.org/5vwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vwq RCSB], [http://www.ebi.ac.uk/pdbsum/5vwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vwq 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=5vwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vwq OCA], [http://pdbe.org/5vwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vwq RCSB], [http://www.ebi.ac.uk/pdbsum/5vwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vwq ProSAT]</span></td></tr>
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	</StructureSection>		</StructureSection>
	[[Category: Aspartate transaminase]]		[[Category: Aspartate transaminase]]
		+	[[Category: Ecoli]]
	[[Category: Lehrer, H]]		[[Category: Lehrer, H]]
	[[Category: Liu, D]]		[[Category: Liu, D]]

OCA: Protected "5vwq" [edit=sysop:move=sysop]

OCA — Wed, 30 Aug 2017 04:15:56 GMT

Protected "5vwq" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:15, 30 August 2017

OCA: New page: ==E.coli Aspartate aminotransferase-(1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid (FCP)== == Structural highlights ==
<table><tr><td colspan='2'>[[5vwq]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VWQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PMP:4-DEOXY-4-AMINOPYRIDOXAL-5-PHOSPHATE'>PMP</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vwo|5vwo]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aspartate_transaminase Aspartate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.1 2.6.1.1] </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=5vwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vwq OCA], [http://pdbe.org/5vwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vwq RCSB], [http://www.ebi.ac.uk/pdbsum/5vwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vwq ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Potent mechanism-based inactivators can be rationally designed against PLP-dependent drug targets, such as ornithine aminotransferase (OAT) or gamma-aminobutyric acid aminotransferase (GABA-AT). An important challenge, however, is the lack of selectivity towards other PLP-dependent off-target enzymes, because of similarities in mechanisms of all PLP-dependent aminotransferase reactions. On the basis of complex crystal structures, we investigate the inactivation mechanism of OAT, a hepatocellular carcinoma (HCC) target, by (1R,3S,4S)-3-amino-4-fluorocyclopentane-1-carboxylic acid (FCP), a known inactivator of GABA-AT. A crystal structure of OAT and FCP showed the formation of a ternary adduct. This adduct can be rationalized as occurring via an enamine mechanism of inactivation similar to that reported for GABA-AT. However, the crystal structure of an off-target PLP-dependent enzyme, aspartate aminotransferase (Asp-AT), in complex with FCP, along with the results of attempted inhibition assays, suggest that FCP is not an inactivator of Asp-AT, but rather an alternate substrate. Turnover of FCP by Asp-AT is also supported by high-resolution mass spectrometry. In comparison to the inactivation mechanisms of FCP against OAT and GABA-AT, the obtained results provide evidence that a desirable selectivity of inactivation could be achieved, taking advantage of subtle structural and mechanistic differences between a drug-target and an off-target enzyme, despite their largely similar substrate binding sites and catalytic mechanisms.

Selective Targeting by a Mechanism-based Inactivator against PLP-Dependent Enzymes: Mechanisms of Inactivation and Alternative Turnover.,Mascarenhas R, Le HV, Clevenger KD, Lehrer HJ, Ringe D, Kelleher NL, Silverman RB, Liu D Biochemistry. 2017 Aug 17. doi: 10.1021/acs.biochem.7b00499. PMID:28816437<ref>PMID:28816437</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5vwq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
TOC
</StructureSection>
[[Category: Aspartate transaminase]]
[[Category: Lehrer, H]]
[[Category: Liu, D]]
[[Category: Mascarenhas, R]]
[[Category: Ringe, D]]
[[Category: 3]]
[[Category: Aspartate aminotransferase]]
[[Category: Mechanism-based inactivator]]
[[Category: Pmp]]
[[Category: Transferase]]