5g0w - Revision history

OCA at 13:34, 26 July 2023

OCA — Wed, 26 Jul 2023 13:34:45 GMT

←Older revision		Revision as of 13:34, 26 July 2023
Line 3:		Line 3:
	<StructureSection load='5g0w' size='340' side='right'caption='[[5g0w]], [[Resolution\|resolution]] 1.79Å' scene=''>		<StructureSection load='5g0w' size='340' side='right'caption='[[5g0w]], [[Resolution\|resolution]] 1.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5g0w]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Myctu Myctu~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G0W OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5G0W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5g0w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G0W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5G0W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9NU:(2S,4S)-N-METHYL-4-[[(2S,3R)-3-[(2-METHYLPROPAN-2-YL)OXY]-2-[[4-(PYRAZOL-1-YLMETHYL)PHENYL]CARBONYLAMINO]BUTANOYL]AMINO]-1-(PHENYLCARBONYL)PYRROLIDINE-2-CARBOXAMIDE'>9NU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 1.79Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5g0s\|5g0s]], [[5g0t\|5g0t]], [[5g0u\|5g0u]], [[5g0v\|5g0v]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9NU:(2S,4S)-N-METHYL-4-[[(2S,3R)-3-[(2-METHYLPROPAN-2-YL)OXY]-2-[[4-(PYRAZOL-1-YLMETHYL)PHENYL]CARBONYLAMINO]BUTANOYL]AMINO]-1-(PHENYLCARBONYL)PYRROLIDINE-2-CARBOXAMIDE'>9NU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=5g0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g0w OCA], [https://pdbe.org/5g0w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5g0w RCSB], [https://www.ebi.ac.uk/pdbsum/5g0w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5g0w ProSAT]</span></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=5g0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g0w OCA], [~~http~~://pdbe.org/5g0w PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5g0w RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5g0w PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5g0w ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/INHA_MYCTU INHA_MYCTU]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Myctu~~]]	+	[[Category: Mycobacterium tuberculosis H37Rv]]
-	[[Category: Breed, J]]	+	[[Category: Breed J]]
-	[[Category: Read~~, J A]]~~	+	[[Category: Read JA]]
-	~~[[Category: Acp enoyl reductase]]~~	+
-	~~[[Category: Del]]~~	+
-	~~[[Category: Dna encoded library]]~~	+
-	~~[[Category: Inha]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Tuberculosis~~]]	+

OCA at 06:34, 13 May 2020

OCA — Wed, 13 May 2020 06:34:06 GMT

←Older revision		Revision as of 06:34, 13 May 2020
Line 1:		Line 1:

	==InhA in complex with a DNA encoded library hit==		==InhA in complex with a DNA encoded library hit==
-	<StructureSection load='5g0w' size='340' side='right' caption='[[5g0w]], [[Resolution\|resolution]] 1.79Å' scene=''>	+	<StructureSection load='5g0w' size='340' side='right'caption='[[5g0w]], [[Resolution\|resolution]] 1.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5g0w]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G0W OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5G0W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5g0w]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G0W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5G0W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9NU:(2S,4S)-N-METHYL-4-[[(2S,3R)-3-[(2-METHYLPROPAN-2-YL)OXY]-2-[[4-(PYRAZOL-1-YLMETHYL)PHENYL]CARBONYLAMINO]BUTANOYL]AMINO]-1-(PHENYLCARBONYL)PYRROLIDINE-2-CARBOXAMIDE'>9NU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9NU:(2S,4S)-N-METHYL-4-[[(2S,3R)-3-[(2-METHYLPROPAN-2-YL)OXY]-2-[[4-(PYRAZOL-1-YLMETHYL)PHENYL]CARBONYLAMINO]BUTANOYL]AMINO]-1-(PHENYLCARBONYL)PYRROLIDINE-2-CARBOXAMIDE'>9NU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5g0s\|5g0s]], [[5g0t\|5g0t]], [[5g0u\|5g0u]], [[5g0v\|5g0v]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5g0s\|5g0s]], [[5g0t\|5g0t]], [[5g0u\|5g0u]], [[5g0v\|5g0v]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=5g0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g0w OCA], [http://pdbe.org/5g0w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g0w RCSB], [http://www.ebi.ac.uk/pdbsum/5g0w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g0w ProSAT]</span></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=5g0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g0w OCA], [http://pdbe.org/5g0w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g0w RCSB], [http://www.ebi.ac.uk/pdbsum/5g0w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g0w ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 18:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 5g0w" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5g0w" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Enoyl-Acyl-Carrier Protein Reductase 3D structures\|Enoyl-Acyl-Carrier Protein Reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Myctu]]
	[[Category: Breed, J]]		[[Category: Breed, J]]
	[[Category: Read, J A]]		[[Category: Read, J A]]

OCA at 18:32, 10 December 2016

OCA — Sat, 10 Dec 2016 18:32:49 GMT

←Older revision		Revision as of 18:32, 10 December 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5g0w is ~~ON HOLD until Paper~~ Publication	+	==InhA in complex with a DNA encoded library hit==
		+	<StructureSection load='5g0w' size='340' side='right' caption='[[5g0w]], [[Resolution\|resolution]] 1.79Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5g0w]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G0W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5G0W FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9NU:(2S,4S)-N-METHYL-4-[[(2S,3R)-3-[(2-METHYLPROPAN-2-YL)OXY]-2-[[4-(PYRAZOL-1-YLMETHYL)PHENYL]CARBONYLAMINO]BUTANOYL]AMINO]-1-(PHENYLCARBONYL)PYRROLIDINE-2-CARBOXAMIDE'>9NU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5g0s\|5g0s]], [[5g0t\|5g0t]], [[5g0u\|5g0u]], [[5g0v\|5g0v]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=5g0w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g0w OCA], [http://pdbe.org/5g0w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g0w RCSB], [http://www.ebi.ac.uk/pdbsum/5g0w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g0w ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Millions of individuals are infected with and die from tuberculosis (TB) each year, and multidrug-resistant (MDR) strains of TB are increasingly prevalent. As such, there is an urgent need to identify novel drugs to treat TB infections. Current frontline therapies include the drug isoniazid, which inhibits the essential NADH-dependent enoyl-acyl-carrier protein (ACP) reductase, InhA. To inhibit InhA, isoniazid must be activated by the catalase-peroxidase KatG. Isoniazid resistance is linked primarily to mutations in the katG gene. Discovery of InhA inhibitors that do not require KatG activation is crucial to combat MDR TB. Multiple discovery efforts have been made against InhA in recent years. Until recently, despite achieving high potency against the enzyme, these efforts have been thwarted by lack of cellular activity. We describe here the use of DNA-encoded X-Chem (DEX) screening, combined with selection of appropriate physical properties, to identify multiple classes of InhA inhibitors with cell-based activity. The utilization of DEX screening allowed the interrogation of very large compound libraries (1011 unique small molecules) against multiple forms of the InhA enzyme in a multiplexed format. Comparison of the enriched library members across various screening conditions allowed the identification of cofactor-specific inhibitors of InhA that do not require activation by KatG, many of which had bactericidal activity in cell-based assays.

-	~~Authors: READ~~, ~~J.A~~., ~~BREED~~, J.	+	Discovery of cofactor-specific, bactericidal Mycobacterium tuberculosis InhA inhibitors using DNA-encoded library technology.,Soutter HH, Centrella P, Clark MA, Cuozzo JW, Dumelin CE, Guie MA, Habeshian S, Keefe AD, Kennedy KM, Sigel EA, Troast DM, Zhang Y, Ferguson AD, Davies G, Stead ER, Breed J, Madhavapeddi P, Read JA Proc Natl Acad Sci U S A. 2016 Dec 6;113(49):E7880-E7889. Epub 2016 Nov 18. PMID:27864515<ref>PMID:27864515</ref>

-	~~Description: InhA in complex with~~ a ~~DNA encoded library hit~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Read, J.A]]~~	+	<div class="pdbe-citations 5g0w" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Breed, J]]		[[Category: Breed, J]]
		+	[[Category: Read, J A]]
		+	[[Category: Acp enoyl reductase]]
		+	[[Category: Del]]
		+	[[Category: Dna encoded library]]
		+	[[Category: Inha]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Tuberculosis]]

OCA: Protected "5g0w" [edit=sysop:move=sysop]

OCA — Tue, 10 May 2016 23:19:36 GMT

Protected "5g0w" [edit=sysop:move=sysop]

←Older revision

Revision as of 23:19, 10 May 2016

OCA: New page: '''Unreleased structure''' The entry 5g0w is ON HOLD until Paper Publication Authors: READ, J.A., BREED, J. Description: InhA in complex with a DNA encoded library hit [[Category: Unre...

OCA — Tue, 10 May 2016 23:19:35 GMT

New page: '''Unreleased structure''' The entry 5g0w is ON HOLD until Paper Publication Authors: READ, J.A., BREED, J. Description: InhA in complex with a DNA encoded library hit [[Category: Unre...

New page

'''Unreleased structure'''

The entry 5g0w is ON HOLD until Paper Publication

Authors: READ, J.A., BREED, J.

Description: InhA in complex with a DNA encoded library hit
[[Category: Unreleased Structures]]
[[Category: Read, J.A]]
[[Category: Breed, J]]