6vb9 - Revision history

OCA at 08:08, 11 October 2023

2023-10-11T08:08:12Z

← Older revision		Revision as of 08:08, 11 October 2023
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	<StructureSection load='6vb9' size='340' side='right'caption='[[6vb9]], [[Resolution\|resolution]] 1.88Å' scene=''>		<StructureSection load='6vb9' size='340' side='right'caption='[[6vb9]], [[Resolution\|resolution]] 1.88Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6vb9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus~~ tuberculosis~~" (zopf 1883) klein 1884~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VB9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VB9 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6vb9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VB9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VB9 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXD:OXALIC+ACID'>OXD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 1.881Å</td></tr>
	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=QVA:~~'>QVA</scene></td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXD:OXALIC+ACID'>OXD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=QVA:(2S,3R)-2-{[(2R)-2-amino-2-carboxyethyl]sulfanyl}-3-hydroxybutanedioic+acid'>QVA</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">aceA_1~~, ~~aceA, ERS007703_00218, ERS023446_00716, ERS027651_01707, EZX46_15490, FDK60_05445, FDK62_09180, SAMEA2682864_01056, SAMEA2683035_00941 (~~[~~https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis"~~ (~~Zopf 1883~~) ~~Klein 1884~~]~~)</td></tr>~~
	~~<tr id='activity~~'>~~<td class="sblockLbl"><b>Activity:~~</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Isocitrate_lyase Isocitrate lyase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.1 4.1.3.1] </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=6vb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vb9 OCA], [https://pdbe.org/6vb9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vb9 RCSB], [https://www.ebi.ac.uk/pdbsum/6vb9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vb9 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=6vb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vb9 OCA], [https://pdbe.org/6vb9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vb9 RCSB], [https://www.ebi.ac.uk/pdbsum/6vb9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vb9 ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/ACEA_MYCTU ACEA_MYCTU] Catalyzes the formation of succinate and glyoxylate from isocitrate, a key step of the glyoxylate cycle. May be involved in the assimilation of one-carbon compounds via the isocitrate lyase-positive serine pathway (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Isocitrate lyase]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Krieger, I V~~]]		[[Category: Mycobacterium tuberculosis]]
	[[Category: ~~Meek, T D~~]]		[[Category: Krieger IV]]
	[[Category: ~~Pham, T V~~]]		[[Category: Meek TD]]
	[[Category: ~~Sacchettini, J C~~]]		[[Category: Pham TV]]
	[[Category: ~~Structural genomic]]~~		[[Category: Sacchettini JC]]
	~~[[Category: Covalent inhibitor]]~~
	~~[[Category: Enzyme]]~~
	~~[[Category: Lyase]]~~
	~~[[Category: Psi-biology]]~~
	~~[[Category: Substrate analog]]~~
	~~[[Category: Tbsgc~~]]

OCA at 06:50, 24 March 2021

2021-03-24T06:50:03Z

← Older revision		Revision as of 06:50, 24 March 2021
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	==Covalent adduct of cis-2,3-epoxysuccinic acid with Isocitrate Lyase-1 from Mycobacterium tuberculosis==		==Covalent adduct of cis-2,3-epoxysuccinic acid with Isocitrate Lyase-1 from Mycobacterium tuberculosis==
	<StructureSection load='6vb9' size='340' side='right'caption='[[6vb9]]' scene=''>		<StructureSection load='6vb9' size='340' side='right'caption='[[6vb9]], [[Resolution\|resolution]] 1.88Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VB9 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6VB9 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6vb9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VB9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VB9 FirstGlance]. <br>
	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6vb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vb9 OCA], [~~http~~://pdbe.org/6vb9 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6vb9 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6vb9 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6vb9 ProSAT]</span></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXD:OXALIC+ACID'>OXD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
			<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=QVA:'>QVA</scene></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">aceA_1, aceA, ERS007703_00218, ERS023446_00716, ERS027651_01707, EZX46_15490, FDK60_05445, FDK62_09180, SAMEA2682864_01056, SAMEA2683035_00941 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Isocitrate_lyase Isocitrate lyase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.3.1 4.1.3.1] </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=6vb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vb9 OCA], [https://pdbe.org/6vb9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vb9 RCSB], [https://www.ebi.ac.uk/pdbsum/6vb9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vb9 ProSAT]</span></td></tr>
	</table>		</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The isocitrate lyases (ICL1/2) are essential enzymes of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. At present, no ICL1/2 inhibitors have progressed to clinical evaluation, despite extensive drug discovery efforts. Herein, we surveyed succinate analogs against ICL1 and found that dicarboxylic acids constrained in their synperiplanar conformations, such as maleic acid, comprise uncompetitive inhibitors of ICL1 and inhibit more potently than their trans-isomers. From this, we identified cis-2,3 epoxysuccinic acid (cis-EpS) as a selective, irreversible covalent inactivator of Mtb ICL1 (kinact/Kinact= (5.0 +/- 1.4) x 10(4) M(-1) s(-1); Kinact = 200 +/- 50 nM), the most potent inactivator of ICL1 yet characterized. Crystallographic and mass spectrometric analysis demonstrated that Cys191 of ICL1 was S-malylated by cis-EpS, and a crystallographic "snapshot" of inactivation lent insight into the chemical mechanism of this inactivation. Proteomic analysis of E. coli lysates showed that cis-EpS selectively labeled plasmid-expressed Mtb ICL1. Consistently, cis-EpS, but not its trans-isomer, inhibited the growth of Mtb under conditions in which ICL function is essential. These findings encourage the development of analogs of cis-2,3-epoxysuccinate as antituberculosis agents.

			Covalent Inactivation of Mycobacterium tuberculosis Isocitrate Lyase by cis-2,3-Epoxy-Succinic Acid.,Pham TV, Mellott DM, Moghadamchargari Z, Chen K, Krieger I, Laganowsky A, Sacchettini JC, Meek TD ACS Chem Biol. 2021 Mar 19;16(3):463-470. doi: 10.1021/acschembio.0c00740. Epub, 2021 Mar 10. PMID:33688722<ref>PMID:33688722</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 6vb9" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Isocitrate lyase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Krieger IV]]		[[Category: Krieger, I V]]
	[[Category: Meek TD]]		[[Category: Meek, T D]]
	[[Category: Pham TV]]		[[Category: Pham, T V]]
	[[Category: Sacchettini JC]]		[[Category: Sacchettini, J C]]
			[[Category: Structural genomic]]
			[[Category: Covalent inhibitor]]
			[[Category: Enzyme]]
			[[Category: Lyase]]
			[[Category: Psi-biology]]
			[[Category: Substrate analog]]
			[[Category: Tbsgc]]

OCA at 06:43, 30 December 2020

2020-12-30T06:43:34Z

← Older revision		Revision as of 06:43, 30 December 2020
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	~~'''Unreleased structure'''~~

	~~The entry 6vb9 is ON HOLD until Paper Publication~~		==Covalent adduct of cis-2,3-epoxysuccinic acid with Isocitrate Lyase-1 from Mycobacterium tuberculosis==
			<StructureSection load='6vb9' size='340' side='right'caption='[[6vb9]]' scene=''>
	~~Authors: Krieger, I.V., Pham, T.V., Meek, T.D., Sacchettini, J.C., TB Structural Genomics Consortium (TBSGC)~~		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VB9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VB9 FirstGlance]. <br>
	~~Description:~~ Covalent adduct of cis-2,3-epoxysuccinic acid with Isocitrate Lyase-1 from Mycobacterium tuberculosis		</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vb9 OCA], [http://pdbe.org/6vb9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vb9 RCSB], [http://www.ebi.ac.uk/pdbsum/6vb9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vb9 ProSAT]</span></td></tr>
	[[~~Category~~: ~~Unreleased Structures~~]]		</table>
	[[~~Category~~: ~~Krieger~~, I.V]]		__TOC__
	[[Category: ~~Meek, T.D~~]]		</StructureSection>
	[[Category: ~~Pham, T.V~~]]		[[Category: Large Structures]]
	[[Category: ~~Sacchettini, J.C~~]]		[[Category: Krieger IV]]
	[[Category: ~~Tb Structural Genomics Consortium (Tbsgc)~~]]		[[Category: Meek TD]]
			[[Category: Pham TV]]
			[[Category: Sacchettini JC]]

OCA at 05:34, 4 March 2020

2020-03-04T05:34:00Z

← Older revision		Revision as of 05:34, 4 March 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 6vb9 is ON HOLD		The entry 6vb9 is ON HOLD until Paper Publication

	Authors: Krieger, I.V., Pham, T.V., Meek, T.D., Sacchettini, J.C., TB Structural Genomics Consortium (TBSGC)		Authors: Krieger, I.V., Pham, T.V., Meek, T.D., Sacchettini, J.C., TB Structural Genomics Consortium (TBSGC)

OCA at 06:48, 1 January 2020

2020-01-01T06:48:15Z

← Older revision		Revision as of 06:48, 1 January 2020
Line 3:		Line 3:
	The entry 6vb9 is ON HOLD		The entry 6vb9 is ON HOLD

	Authors: Krieger, I.V., Pham, T.V., Meek, T.D., Sacchettini, J.C.		Authors: Krieger, I.V., Pham, T.V., Meek, T.D., Sacchettini, J.C., TB Structural Genomics Consortium (TBSGC)

	Description: Covalent adduct of cis-2,3-epoxysuccinic acid with Isocitrate Lyase-1 from Mycobacterium tuberculosis		Description: Covalent adduct of cis-2,3-epoxysuccinic acid with Isocitrate Lyase-1 from Mycobacterium tuberculosis
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	[[Category: Pham, T.V]]		[[Category: Pham, T.V]]
	[[Category: Sacchettini, J.C]]		[[Category: Sacchettini, J.C]]
			[[Category: Tb Structural Genomics Consortium (Tbsgc)]]

OCA: Protected "6vb9" [edit=sysop:move=sysop]

2019-12-25T07:38:28Z

Protected "6vb9" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:38, 25 December 2019
(No difference)

OCA: New page: '''Unreleased structure''' The entry 6vb9 is ON HOLD Authors: Krieger, I.V., Pham, T.V., Meek, T.D., Sacchettini, J.C. Description: Covalent adduct of cis-2,3-epoxysuccinic acid with I...

2019-12-25T07:38:26Z

New page: '''Unreleased structure''' The entry 6vb9 is ON HOLD Authors: Krieger, I.V., Pham, T.V., Meek, T.D., Sacchettini, J.C. Description: Covalent adduct of cis-2,3-epoxysuccinic acid with I...

New page

'''Unreleased structure'''

The entry 6vb9 is ON HOLD

Authors: Krieger, I.V., Pham, T.V., Meek, T.D., Sacchettini, J.C.

Description: Covalent adduct of cis-2,3-epoxysuccinic acid with Isocitrate Lyase-1 from Mycobacterium tuberculosis
[[Category: Unreleased Structures]]
[[Category: Krieger, I.V]]
[[Category: Meek, T.D]]
[[Category: Pham, T.V]]
[[Category: Sacchettini, J.C]]