5nae - Revision history

OCA at 12:42, 15 November 2023

OCA — Wed, 15 Nov 2023 12:42:48 GMT

←Older revision		Revision as of 12:42, 15 November 2023
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	==Pseudomonas fluorescens kynurenine 3-monooxygenase (KMO) in complex with 3-{5-chloro-2-oxo-6-[(1R)-1-(pyridin-2-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl}propanoic acid==		==Pseudomonas fluorescens kynurenine 3-monooxygenase (KMO) in complex with 3-{5-chloro-2-oxo-6-[(1R)-1-(pyridin-2-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl}propanoic acid==
-	<StructureSection load='5nae' size='340' side='right' caption='[[5nae]], [[Resolution\|resolution]] 1.76Å' scene=''>	+	<StructureSection load='5nae' size='340' side='right'caption='[[5nae]], [[Resolution\|resolution]] 1.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nae]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~"bacillus_fluorescens_liquefaciens"_flugge_1886 "bacillus~~ fluorescens ~~liquefaciens" flugge 1886~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NAE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5NAE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nae]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_fluorescens Pseudomonas fluorescens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NAE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8R8:3-[5-chloranyl-2-oxidanylidene-6-[(1~{R})-1-pyridin-2-ylethoxy]-1,3-benzoxazol-3-yl]propanoic+acid'>8R8</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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]] 1.76Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">kmo, qbsG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=294 "Bacillus fluorescens liquefaciens" Flugge 1886])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8R8:3-[5-chloranyl-2-oxidanylidene-6-[(1~{R})-1-pyridin-2-ylethoxy]-1,3-benzoxazol-3-yl]propanoic+acid'>8R8</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Kynurenine_3-monooxygenase Kynurenine 3-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.9 1.14.13.9] </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=5nae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nae OCA], [https://pdbe.org/5nae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nae RCSB], [https://www.ebi.ac.uk/pdbsum/5nae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nae 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=5nae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nae OCA], [~~http~~://pdbe.org/5nae PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5nae RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5nae PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5nae ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KMO_PSEFL KMO_PSEFL]] Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Probably required for the synthesis of quinolinic acid and the siderophore quinolobactin.	+	[https://www.uniprot.org/uniprot/KMO_PSEFL KMO_PSEFL] Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Probably required for the synthesis of quinolinic acid and the siderophore quinolobactin.
	<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 5nae" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5nae" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Monooxygenase 3D structures\|Monooxygenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bacillus fluorescens liquefaciens flugge 1886~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Kynurenine 3-monooxygenase~~]]	+	[[Category: Pseudomonas fluorescens]]
-	[[Category: Rowland, P]]	+	[[Category: Rowland P]]
-	~~[[Category: Kmo]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 08:47, 16 November 2017

OCA — Thu, 16 Nov 2017 08:47:29 GMT

←Older revision		Revision as of 08:47, 16 November 2017
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-	'''Unreleased structure'''

-	~~The entry~~ 5nae is ~~ON HOLD until Paper~~ Publication	+	==Pseudomonas fluorescens kynurenine 3-monooxygenase (KMO) in complex with 3-{5-chloro-2-oxo-6-[(1R)-1-(pyridin-2-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl}propanoic acid==
		+	<StructureSection load='5nae' size='340' side='right' caption='[[5nae]], [[Resolution\|resolution]] 1.76Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5nae]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_fluorescens_liquefaciens"_flugge_1886 "bacillus fluorescens liquefaciens" flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NAE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NAE FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8R8:3-[5-chloranyl-2-oxidanylidene-6-[(1~{R})-1-pyridin-2-ylethoxy]-1,3-benzoxazol-3-yl]propanoic+acid'>8R8</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">kmo, qbsG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=294 "Bacillus fluorescens liquefaciens" Flugge 1886])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Kynurenine_3-monooxygenase Kynurenine 3-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.9 1.14.13.9] </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=5nae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nae OCA], [http://pdbe.org/5nae PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nae RCSB], [http://www.ebi.ac.uk/pdbsum/5nae PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nae ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KMO_PSEFL KMO_PSEFL]] Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Probably required for the synthesis of quinolinic acid and the siderophore quinolobactin.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Kynurenine-3-monooxygenase (KMO) is a key FAD-dependent enzyme of tryptophan metabolism. In animal models, KMO inhibition has shown benefit in neurodegenerative diseases such as Huntington's and Alzheimer's. Most recently it has been identified as a target for acute pancreatitis multiple organ dysfunction syndrome (AP-MODS); a devastating inflammatory condition with a mortality rate in excess of 20%. Here we report and dissect the molecular mechanism of action of three classes of KMO inhibitors with differentiated binding modes and kinetics. Two novel inhibitor classes trap the catalytic flavin in a previously unobserved tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production seen with previous substrate site inhibitors. These structural and mechanistic insights culminated in GSK065(C1) and GSK366(C2), molecules suitable for preclinical evaluation. Moreover, revising the repertoire of flavin dynamics in this enzyme class offers exciting new opportunities for inhibitor design.

-	~~Authors~~:	+	Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase.,Hutchinson JP, Rowland P, Taylor MRD, Christodoulou EM, Haslam C, Hobbs CI, Holmes DS, Homes P, Liddle J, Mole DJ, Uings I, Walker AL, Webster SP, Mowat CG, Chung CW Nat Commun. 2017 Jun 12;8:15827. doi: 10.1038/ncomms15827. PMID:28604669<ref>PMID:28604669</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5nae" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Bacillus fluorescens liquefaciens flugge 1886]]
		+	[[Category: Kynurenine 3-monooxygenase]]
		+	[[Category: Rowland, P]]
		+	[[Category: Kmo]]
		+	[[Category: Oxidoreductase]]

OCA at 09:50, 5 April 2017

OCA — Wed, 05 Apr 2017 09:50:21 GMT

←Older revision		Revision as of 09:50, 5 April 2017
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5nae is ON HOLD	+	The entry 5nae is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Thu, 09 Mar 2017 12:21:22 GMT

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

←Older revision

Revision as of 12:21, 9 March 2017

OCA: New page: '''Unreleased structure''' The entry 5nae is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Thu, 09 Mar 2017 12:21:21 GMT

New page: '''Unreleased structure''' The entry 5nae is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5nae is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]