6vo2 - Revision history

OCA at 08:15, 11 October 2023

OCA — Wed, 11 Oct 2023 08:15:55 GMT

←Older revision		Revision as of 08:15, 11 October 2023
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	<StructureSection load='6vo2' size='340' side='right'caption='[[6vo2]], [[Resolution\|resolution]] 1.59Å' scene=''>		<StructureSection load='6vo2' size='340' side='right'caption='[[6vo2]], [[Resolution\|resolution]] 1.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6vo2]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus~~ aureus~~" (rosenbach 1884) zopf 1885~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VO2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6VO2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vo2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VO2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VO2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=R67:3-(methylsulfonyl)-2-oxopropanoic+acid'>R67</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]] 1.59Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ilvC, DB727_12700, E4U00_11130, ERS072840_02559, NCTC6133_02793, NCTC7878_02786, NCTC7988_02129 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=R67:3-(methylsulfonyl)-2-oxopropanoic+acid'>R67</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ketol-acid_reductoisomerase Ketol-acid reductoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.86 1.1.1.86] </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=6vo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vo2 OCA], [https://pdbe.org/6vo2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vo2 RCSB], [https://www.ebi.ac.uk/pdbsum/6vo2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vo2 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=6vo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vo2 OCA], [~~http~~://pdbe.org/6vo2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6vo2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6vo2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6vo2 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~A0A145BYP4_STAAU A0A145BYP4_STAAU]~~] Involved in the biosynthesis of branched-chain amino acids (BCAA). Catalyzes an alkyl-migration followed by a ketol-acid reduction of (S)-2-acetolactate (S2AL) to yield (R)-2,3-dihydroxy-isovalerate. In the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl migration to produce 3-hydroxy-3-methyl-2-ketobutyrate (HMKB). In the reductase reaction, this 2-ketoacid undergoes a metal-dependent reduction by NADPH to yield (R)-2,3-dihydroxy-isovalerate.[HAMAP-Rule:MF_00435~~][SAAS:SAAS00826005~~]	+	[https://www.uniprot.org/uniprot/ILVC_STAA8 ILVC_STAA8] Involved in the biosynthesis of branched-chain amino acids (BCAA). Catalyzes an alkyl-migration followed by a ketol-acid reduction of (S)-2-acetolactate (S2AL) to yield (R)-2,3-dihydroxy-isovalerate. In the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl migration to produce 3-hydroxy-3-methyl-2-ketobutyrate (HMKB). In the reductase reaction, this 2-ketoacid undergoes a metal-dependent reduction by NADPH to yield (R)-2,3-dihydroxy-isovalerate.[HAMAP-Rule:MF_00435]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6vo2" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6vo2" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ketol-acid reductoisomerase 3D structures\|Ketol-acid reductoisomerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Ketol-acid reductoisomerase]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Bayaraa, T~~]]	+	[[Category: Staphylococcus aureus]]
-	[[Category: ~~Guddat, L W~~]]	+	[[Category: Bayaraa T]]
-	[[Category: ~~Patel, K M~~]]	+	[[Category: Guddat LW]]
-	[[Category: ~~Complex]]~~	+	[[Category: Patel KM]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Metal binding protein]]~~	+
-	~~[[Category: Reductoisomerase~~]]	+

OCA at 14:39, 8 July 2020

OCA — Wed, 08 Jul 2020 14:39:02 GMT

←Older revision		Revision as of 14:39, 8 July 2020
Line 3:		Line 3:
	<StructureSection load='6vo2' size='340' side='right'caption='[[6vo2]], [[Resolution\|resolution]] 1.59Å' scene=''>		<StructureSection load='6vo2' size='340' side='right'caption='[[6vo2]], [[Resolution\|resolution]] 1.59Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6vo2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VO2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VO2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vo2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VO2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VO2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=R67:3-(methylsulfonyl)-2-oxopropanoic+acid'>R67</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=R67:3-(methylsulfonyl)-2-oxopropanoic+acid'>R67</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ilvC, DB727_12700, E4U00_11130, ERS072840_02559, NCTC6133_02793, NCTC7878_02786, NCTC7988_02129 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ketol-acid_reductoisomerase Ketol-acid reductoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.86 1.1.1.86] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ketol-acid_reductoisomerase Ketol-acid reductoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.86 1.1.1.86] </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=6vo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vo2 OCA], [http://pdbe.org/6vo2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vo2 RCSB], [http://www.ebi.ac.uk/pdbsum/6vo2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vo2 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=6vo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vo2 OCA], [http://pdbe.org/6vo2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vo2 RCSB], [http://www.ebi.ac.uk/pdbsum/6vo2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vo2 ProSAT]</span></td></tr>

OCA at 06:58, 8 April 2020

OCA — Wed, 08 Apr 2020 06:58:58 GMT

←Older revision		Revision as of 06:58, 8 April 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6vo2 is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of Staphylococcus aureus ketol-acid reductoisomerase in complex with Mg, NADPH and inhibitor.==
		+	<StructureSection load='6vo2' size='340' side='right'caption='[[6vo2]], [[Resolution\|resolution]] 1.59Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6vo2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VO2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VO2 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=R67:3-(methylsulfonyl)-2-oxopropanoic+acid'>R67</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ketol-acid_reductoisomerase Ketol-acid reductoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.86 1.1.1.86] </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=6vo2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vo2 OCA], [http://pdbe.org/6vo2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vo2 RCSB], [http://www.ebi.ac.uk/pdbsum/6vo2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vo2 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/A0A145BYP4_STAAU A0A145BYP4_STAAU]] Involved in the biosynthesis of branched-chain amino acids (BCAA). Catalyzes an alkyl-migration followed by a ketol-acid reduction of (S)-2-acetolactate (S2AL) to yield (R)-2,3-dihydroxy-isovalerate. In the isomerase reaction, S2AL is rearranged via a Mg-dependent methyl migration to produce 3-hydroxy-3-methyl-2-ketobutyrate (HMKB). In the reductase reaction, this 2-ketoacid undergoes a metal-dependent reduction by NADPH to yield (R)-2,3-dihydroxy-isovalerate.[HAMAP-Rule:MF_00435][SAAS:SAAS00826005]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway, is a potential drug target for bacterial infections including Mycobacterium tuberculosis . Here, we have screened the Medicines for Malaria Venture Pathogen Box against purified M. tuberculosis ( Mt ) KARI and identified two compounds that have K i values below 200 nM. In Mt cell susceptibility assays one of these compounds exhibited an IC 50 value of 0.8 muM. Co-crystallization of this compound, 3-((methylsulfonyl)methyl)-2 H -benzo[ b ][1,4]oxazin-2-one (MMV553002), in complex with Staphylococcus aureus KARI, which has 56% identity with Mt KARI, NADPH and Mg 2+ yielded a structure to 1.72 A resolution. However, only a hydrolyzed product of the inhibitor ( i.e. 3-(methylsulfonyl)-2-oxopropanic acid, missing the 2-aminophenol attachment) is observed in the active site. Surprisingly, Mt cell susceptibility assays showed that the 2-aminophenol product is largely responsible for the anti-TB activity of the parent compound. Thus, we have identified 3-(methylsulfonyl)-2-oxopropanic acid is a potent KARI inhibitor that could be further explored as a potential biocidal agent and we have shown 2-aminophenol, as an anti-TB drug lead, especially given it has low toxicity against human cells. The study highlights that careful analysis of broad screening assays is required to correctly interpret cell-based activity data.

-	~~Authors~~:	+	Discovery, synthesis and evaluation of a novel ketol-acid reductoisomerase inhibitor.,Bayaraa T, Kurz JL, Patel KM, Hussein WM, Bilyj JK, West NP, Schenk G, McGeary RP, Guddat LW Chemistry. 2020 Mar 21. doi: 10.1002/chem.202000899. PMID:32198779<ref>PMID:32198779</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6vo2" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Ketol-acid reductoisomerase]]
		+	[[Category: Large Structures]]
		+	[[Category: Bayaraa, T]]
		+	[[Category: Guddat, L W]]
		+	[[Category: Patel, K M]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Metal binding protein]]
		+	[[Category: Reductoisomerase]]

OCA at 05:35, 4 March 2020

OCA — Wed, 04 Mar 2020 05:35:15 GMT

←Older revision		Revision as of 05:35, 4 March 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6vo2 is ON HOLD	+	The entry 6vo2 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6vo2" [edit=sysop:move=sysop]

OCA — Wed, 05 Feb 2020 06:22:34 GMT

Protected "6vo2" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:22, 5 February 2020

OCA: New page: '''Unreleased structure''' The entry 6vo2 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 05 Feb 2020 06:22:32 GMT

New page: '''Unreleased structure''' The entry 6vo2 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6vo2 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]