6w44 - Revision history

OCA at 14:16, 18 October 2023

2023-10-18T14:16:31Z

←Older revision		Revision as of 14:16, 18 October 2023
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	<StructureSection load='6w44' size='340' side='right'caption='[[6w44]], [[Resolution\|resolution]] 1.64Å' scene=''>		<StructureSection load='6w44' size='340' side='right'caption='[[6w44]], [[Resolution\|resolution]] 1.64Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6w44]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W44 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6w44]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W44 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>~~, ~~<scene name='pdbligand=SLJ:5-~~[~~methyl-~~[~~(2-propoxypyridin-3-yl)methyl~~]~~amino~~]~~-2~{H}-indazole-3-carboxylic+acid'>SLJ</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]] 1.64Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>HAO1, GOX1, HAOX1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</td~~><~~/tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=SLJ:5-[methyl-[(2-propoxypyridin-3-yl)methyl]amino]-2~{H}-indazole-3-carboxylic+acid'>SLJ</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>~~[~~https://en.wikipedia.org/wiki/~~(~~S)-~~2-~~hydroxy~~-~~acid_oxidase (S~~)-2-~~hydroxy~~-acid ~~oxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.3.15 1.1.3.15]~~ </~~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=6w44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w44 OCA], [https://pdbe.org/6w44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w44 RCSB], [https://www.ebi.ac.uk/pdbsum/6w44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w44 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=6w44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w44 OCA], [https://pdbe.org/6w44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w44 RCSB], [https://www.ebi.ac.uk/pdbsum/6w44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w44 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/HAOX1_HUMAN HAOX1_HUMAN]] Has 2-hydroxyacid oxidase activity. Most active on the 2-carbon substrate glycolate, but is also active on 2-hydroxy fatty acids, with high activity towards 2-hydroxy palmitate and 2-hydroxy octanoate.	+	[https://www.uniprot.org/uniprot/HAOX1_HUMAN HAOX1_HUMAN] Has 2-hydroxyacid oxidase activity. Most active on the 2-carbon substrate glycolate, but is also active on 2-hydroxy fatty acids, with high activity towards 2-hydroxy palmitate and 2-hydroxy octanoate.
	<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 6w44" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6w44" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Glycolate oxidase 3D structures\|Glycolate oxidase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ferguson~~, A D]]~~	+	[[Category: Ferguson AD]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 10:15, 19 May 2021

2021-05-19T10:15:06Z

←Older revision		Revision as of 10:15, 19 May 2021
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	==Crystal structure of HAO1 in complex with indazole acid inhibitor - compound 4==		==Crystal structure of HAO1 in complex with indazole acid inhibitor - compound 4==
-	<StructureSection load='6w44' size='340' side='right'caption='[[6w44]]' scene=''>	+	<StructureSection load='6w44' size='340' side='right'caption='[[6w44]], [[Resolution\|resolution]] 1.64Å' 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=6W44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W44 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6w44]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W44 FirstGlance]. <br>
-	</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=6w44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w44 OCA], [https://pdbe.org/6w44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w44 RCSB], [https://www.ebi.ac.uk/pdbsum/6w44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w44 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=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=SLJ:5-[methyl-[(2-propoxypyridin-3-yl)methyl]amino]-2~{H}-indazole-3-carboxylic+acid'>SLJ</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HAO1, GOX1, HAOX1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/(S)-2-hydroxy-acid_oxidase (S)-2-hydroxy-acid oxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.3.15 1.1.3.15] </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=6w44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w44 OCA], [https://pdbe.org/6w44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w44 RCSB], [https://www.ebi.ac.uk/pdbsum/6w44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w44 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/HAOX1_HUMAN HAOX1_HUMAN]] Has 2-hydroxyacid oxidase activity. Most active on the 2-carbon substrate glycolate, but is also active on 2-hydroxy fatty acids, with high activity towards 2-hydroxy palmitate and 2-hydroxy octanoate.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibition of hydroxy acid oxidase 1 (HAO1) is a strategy to mitigate the accumulation of toxic oxalate that results from reduced activity of alanine-glyoxylate aminotransferase (AGXT) in primary hyperoxaluria 1 (PH1) patients. DNA-Encoded Chemical Library (DECL) screening provided two novel chemical series of potent HAO1 inhibitors, represented by compounds 3-6. Compound 5 was further optimized via various structure-activity relationship (SAR) exploration methods to 29, a compound with improved potency and absorption, distribution, metabolism, and excretion (ADME)/pharmacokinetic (PK) properties. Since carboxylic acid-containing compounds are often poorly permeable and have potential active glucuronide metabolites, we undertook a brief, initial exploration of acid replacements with the aim of identifying non-acid-containing HAO1 inhibitors. Structure-based drug design initiated with Compound 5 led to the identification of a nonacid inhibitor of HAO1, 31, which has weaker potency and increased permeability.
		+
		+	Discovery of Novel, Potent Inhibitors of Hydroxy Acid Oxidase 1 (HAO1) Using DNA-Encoded Chemical Library Screening.,Lee ECY, McRiner AJ, Georgiadis KE, Liu J, Wang Z, Ferguson AD, Levin B, von Rechenberg M, Hupp CD, Monteiro MI, Keefe AD, Olszewski A, Eyermann CJ, Centrella P, Liu Y, Arora S, Cuozzo JW, Zhang Y, Clark MA, Huguet C, Kohlmann A J Med Chem. 2021 May 6. doi: 10.1021/acs.jmedchem.0c02271. PMID:33955740<ref>PMID:33955740</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6w44" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ferguson AD]]	+	[[Category: Ferguson, A D]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Oxidoreductase]]

OCA at 09:17, 12 May 2021

2021-05-12T09:17:32Z

←Older revision		Revision as of 09:17, 12 May 2021
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-	'''Unreleased structure'''

-	~~The entry 6w44 is ON HOLD until Sep 10 2022~~	+	==Crystal structure of HAO1 in complex with indazole acid inhibitor - compound 4==
-		+	<StructureSection load='6w44' size='340' side='right'caption='[[6w44]]' scene=''>
-	~~Authors: Ferguson, A.D.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W44 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W44 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of HAO1 in complex with indazole acid inhibitor -compound 4	+	</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=6w44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w44 OCA], [https://pdbe.org/6w44 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w44 RCSB], [https://www.ebi.ac.uk/pdbsum/6w44 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w44 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: Ferguson~~, A.D~~]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Ferguson AD]]

OCA at 04:07, 28 April 2021

2021-04-28T04:07:33Z

←Older revision		Revision as of 04:07, 28 April 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6w44 is ON HOLD until ~~Paper Publication~~	+	The entry 6w44 is ON HOLD until Sep 10 2022

	Authors: Ferguson, A.D.		Authors: Ferguson, A.D.

OCA at 05:54, 21 April 2021

2021-04-21T05:54:05Z

←Older revision		Revision as of 05:54, 21 April 2021
Line 5:		Line 5:
	Authors: Ferguson, A.D.		Authors: Ferguson, A.D.

-	Description: Crystal ~~Structure~~ of HAO1 in complex with inhibitor ~~X12395~~	+	Description: Crystal structure of HAO1 in complex with indazole acid inhibitor -compound 4
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Ferguson, A.D]]		[[Category: Ferguson, A.D]]

OCA: Protected "6w44" [edit=sysop:move=sysop]

2020-03-18T08:33:37Z

Protected "6w44" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:33, 18 March 2020

OCA: New page: '''Unreleased structure''' The entry 6w44 is ON HOLD until Paper Publication Authors: Ferguson, A.D. Description: Crystal Structure of HAO1 in complex with inhibitor X12395 [[Category:...

2020-03-18T08:33:36Z

New page: '''Unreleased structure''' The entry 6w44 is ON HOLD until Paper Publication Authors: Ferguson, A.D. Description: Crystal Structure of HAO1 in complex with inhibitor X12395 [[Category:...

New page

'''Unreleased structure'''

The entry 6w44 is ON HOLD until Paper Publication

Authors: Ferguson, A.D.

Description: Crystal Structure of HAO1 in complex with inhibitor X12395
[[Category: Unreleased Structures]]
[[Category: Ferguson, A.D]]