5ouk - Revision history

OCA at 01:24, 28 December 2023

OCA — Thu, 28 Dec 2023 01:24:52 GMT

←Older revision		Revision as of 01:24, 28 December 2023
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	==Crystal structure of human AKR1B1 complexed with NADP+ and compound 41==		==Crystal structure of human AKR1B1 complexed with NADP+ and compound 41==
-	<StructureSection load='5ouk' size='340' side='right' caption='[[5ouk]], [[Resolution\|resolution]] 0.96Å' scene=''>	+	<StructureSection load='5ouk' size='340' side='right'caption='[[5ouk]], [[Resolution\|resolution]] 0.96Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ouk]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OUK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5OUK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ouk]] 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=5OUK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OUK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AVT:2-[9-fluoranyl-5-(4-methoxyphenyl)-3-methyl-1-oxidanylidene-pyrimido[4,5-c]quinolin-2-yl]ethanoic+acid'>AVT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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]] 0.959Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4igs\|4igs]], [[5ou0\|5ou0]], [[5ouj\|5ouj]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AVT:2-[9-fluoranyl-5-(4-methoxyphenyl)-3-methyl-1-oxidanylidene-pyrimido[4,5-c]quinolin-2-yl]ethanoic+acid'>AVT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AKR1B1, ALDR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5ouk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ouk OCA], [https://pdbe.org/5ouk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ouk RCSB], [https://www.ebi.ac.uk/pdbsum/5ouk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ouk ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aldehyde_reductase Aldehyde reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.21 1.1.1.21] </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=5ouk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ouk OCA], [~~http~~://pdbe.org/5ouk PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ouk RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ouk PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ouk ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/ALDR_HUMAN ALDR_HUMAN]] Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.	+	[https://www.uniprot.org/uniprot/ALDR_HUMAN ALDR_HUMAN] Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5ouk" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5ouk" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aldose reductase 3D structures\|Aldose reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Aldehyde reductase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Cousido-Siah, A]]	+	[[Category: Cousido-Siah A]]
-	[[Category: Metwally, K]]	+	[[Category: Metwally K]]
-	[[Category: Mitschler, A]]	+	[[Category: Mitschler A]]
-	[[Category: Podjarny, A]]	+	[[Category: Podjarny A]]
-	[[Category: Ruiz~~, F X]]~~	+	[[Category: Ruiz FX]]
-	~~[[Category: Aldo-keto reductase]]~~	+
-	~~[[Category: Alpha-beta tim barrel]]~~	+
-	~~[[Category: Cytosol]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 08:16, 6 March 2019

OCA — Wed, 06 Mar 2019 08:16:50 GMT

←Older revision		Revision as of 08:16, 6 March 2019
Line 1:		Line 1:

	==Crystal structure of human AKR1B1 complexed with NADP+ and compound 41==		==Crystal structure of human AKR1B1 complexed with NADP+ and compound 41==
-	<StructureSection load='5ouk' size='340' side='right' caption='[[5ouk]], [[Resolution\|resolution]] 0.96Å' scene=''>	+	<StructureSection load='5ouk' size='340' side='right' caption='[[5ouk]], [[Resolution\|resolution]] 0.96Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ouk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OUK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OUK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ouk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OUK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OUK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AVT:2-[5-[4-~~(dioxidanyl~~)~~phenyl]-9-fluoranyl~~-3-methyl-1-oxidanylidene-pyrimido[4,5-c]quinolin-2-yl]ethanoic+acid'>AVT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AVT:2-[9-fluoranyl-5-(4-methoxyphenyl)-3-methyl-1-oxidanylidene-pyrimido[4,5-c]quinolin-2-yl]ethanoic+acid'>AVT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4igs\|4igs]], [[5ou0\|5ou0]], [[5ouj\|5ouj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4igs\|4igs]], [[5ou0\|5ou0]], [[5ouj\|5ouj]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AKR1B1, ALDR1 ([http://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'>[http://en.wikipedia.org/wiki/Aldehyde_reductase Aldehyde reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.21 1.1.1.21] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aldehyde_reductase Aldehyde reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.21 1.1.1.21] </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=5ouk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ouk OCA], [http://pdbe.org/5ouk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ouk RCSB], [http://www.ebi.ac.uk/pdbsum/5ouk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ouk 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=5ouk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ouk OCA], [http://pdbe.org/5ouk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ouk RCSB], [http://www.ebi.ac.uk/pdbsum/5ouk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ouk ProSAT]</span></td></tr>
Line 25:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Aldehyde reductase]]		[[Category: Aldehyde reductase]]
		+	[[Category: Human]]
	[[Category: Cousido-Siah, A]]		[[Category: Cousido-Siah, A]]
	[[Category: Metwally, K]]		[[Category: Metwally, K]]

OCA at 06:09, 9 May 2018

OCA — Wed, 09 May 2018 06:09:15 GMT

←Older revision		Revision as of 06:09, 9 May 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5ouk is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of human AKR1B1 complexed with NADP+ and compound 41==
		+	<StructureSection load='5ouk' size='340' side='right' caption='[[5ouk]], [[Resolution\|resolution]] 0.96Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5ouk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OUK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OUK FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AVT:2-[5-[4-(dioxidanyl)phenyl]-9-fluoranyl-3-methyl-1-oxidanylidene-pyrimido[4,5-c]quinolin-2-yl]ethanoic+acid'>AVT</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4igs\|4igs]], [[5ou0\|5ou0]], [[5ouj\|5ouj]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aldehyde_reductase Aldehyde reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.21 1.1.1.21] </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=5ouk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ouk OCA], [http://pdbe.org/5ouk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ouk RCSB], [http://www.ebi.ac.uk/pdbsum/5ouk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ouk ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ALDR_HUMAN ALDR_HUMAN]] Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human aldose reductase (AKR1B1, AR) is a key enzyme of the polyol pathway, catalyzing the reduction of glucose to sorbitol at high glucose concentrations, as those found in diabetic condition. Indeed, AKR1B1 overexpression is related to diabetes secondary complications and, in some cases, with cancer. For many years, research has been focused on finding new AKR1B1 inhibitors (ARIs) to overcome these diseases. Despite the efforts, most of the new drug candidates failed because of their poor pharmacokinetic properties and/or unacceptable side effects. Here we report the synthesis of a series of 1-oxopyrimido[4,5-c]quinoline-2-acetic acid derivatives as novel ARIs. IC50 assays and X-ray crystallographic studies proved that these compounds are promising hits for further drug development, with high potency and selectivity against AKR1B1. Based on the determined X-ray structures with hit-to-lead compounds, we designed and synthesized a second series that yielded lead compound 68 (Ki(app)vs. AKR1B1=73nM). These compounds are related to the previously reported 2-aminopyrimido[4,5-c]quinolin-1(2H)-ones, which exhibit antimitotic activity. Regardless of their similarity, the 2-amino compounds are unable to inhibit AKR1B1 while the 2-acetic acid derivatives are not cytotoxic against fibrosarcoma HT-1080cells. Thus, the replacement of the amino group by an acetic acid moiety changes their biological activity, improving their potency as ARIs.

-	~~Authors: Cousido~~-~~Siah~~, A., ~~Ruiz~~, ~~F.X.~~, Mitschler, A., ~~Metwally~~, K., ~~Podjarny~~, A.	+	Design, synthesis, structure-activity relationships and X-ray structural studies of novel 1-oxopyrimido[4,5-c]quinoline-2-acetic acid derivatives as selective and potent inhibitors of human aldose reductase.,Crespo I, Gimenez-Dejoz J, Porte S, Cousido-Siah A, Mitschler A, Podjarny A, Pratsinis H, Kletsas D, Pares X, Ruiz FX, Metwally K, Farres J Eur J Med Chem. 2018 Apr 12;152:160-174. doi: 10.1016/j.ejmech.2018.04.015. PMID:29705708<ref>PMID:29705708</ref>

-	~~Description: Crystal structure~~ of ~~human AKR1B1 complexed with NADP+ and compound 41~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Metwally, K]]~~	+	<div class="pdbe-citations 5ouk" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Ruiz, F.X~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Aldehyde reductase]]
	[[Category: Cousido-Siah, A]]		[[Category: Cousido-Siah, A]]
		+	[[Category: Metwally, K]]
	[[Category: Mitschler, A]]		[[Category: Mitschler, A]]
	[[Category: Podjarny, A]]		[[Category: Podjarny, A]]
		+	[[Category: Ruiz, F X]]
		+	[[Category: Aldo-keto reductase]]
		+	[[Category: Alpha-beta tim barrel]]
		+	[[Category: Cytosol]]
		+	[[Category: Oxidoreductase]]

OCA at 06:59, 10 January 2018

OCA — Wed, 10 Jan 2018 06:59:04 GMT

←Older revision		Revision as of 06:59, 10 January 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Cousido-Siah, A., Ruiz, F.X., Mitschler, A., Metwally, K., Podjarny, A.		Authors: Cousido-Siah, A., Ruiz, F.X., Mitschler, A., Metwally, K., Podjarny, A.
Line 7:		Line 7:
	Description: Crystal structure of human AKR1B1 complexed with NADP+ and compound 41		Description: Crystal structure of human AKR1B1 complexed with NADP+ and compound 41
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Cousido-Siah, A]]
-	[[Category: Mitschler, A]]
	[[Category: Metwally, K]]		[[Category: Metwally, K]]
	[[Category: Ruiz, F.X]]		[[Category: Ruiz, F.X]]
		+	[[Category: Cousido-Siah, A]]
		+	[[Category: Mitschler, A]]
	[[Category: Podjarny, A]]		[[Category: Podjarny, A]]

OCA at 07:58, 4 October 2017

OCA — Wed, 04 Oct 2017 07:58:32 GMT

←Older revision		Revision as of 07:58, 4 October 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5ouk is ON HOLD ~~until sometime in the future~~	+	The entry 5ouk is ON HOLD

	Authors: Cousido-Siah, A., Ruiz, F.X., Mitschler, A., Metwally, K., Podjarny, A.		Authors: Cousido-Siah, A., Ruiz, F.X., Mitschler, A., Metwally, K., Podjarny, A.

-	Description: Crystal structure of human AKR1B1 complexed with NADP+ and compound 39	+	Description: Crystal structure of human AKR1B1 complexed with NADP+ and compound 41
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Podjarny, A]]
-	[[Category: Metwally, K]]
-	[[Category: Mitschler, A]]
	[[Category: Cousido-Siah, A]]		[[Category: Cousido-Siah, A]]
		+	[[Category: Mitschler, A]]
		+	[[Category: Metwally, K]]
	[[Category: Ruiz, F.X]]		[[Category: Ruiz, F.X]]
		+	[[Category: Podjarny, A]]

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

OCA — Wed, 27 Sep 2017 12:52:10 GMT

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

←Older revision

Revision as of 12:52, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5ouk is ON HOLD until sometime in the future Authors: Cousido-Siah, A., Ruiz, F.X., Mitschler, A., Metwally, K., Podjarny, A. Description: Crystal ...

OCA — Wed, 27 Sep 2017 12:52:08 GMT

New page: '''Unreleased structure''' The entry 5ouk is ON HOLD until sometime in the future Authors: Cousido-Siah, A., Ruiz, F.X., Mitschler, A., Metwally, K., Podjarny, A. Description: Crystal ...

New page

'''Unreleased structure'''

The entry 5ouk is ON HOLD until sometime in the future

Authors: Cousido-Siah, A., Ruiz, F.X., Mitschler, A., Metwally, K., Podjarny, A.

Description: Crystal structure of human AKR1B1 complexed with NADP+ and compound 39
[[Category: Unreleased Structures]]
[[Category: Podjarny, A]]
[[Category: Metwally, K]]
[[Category: Mitschler, A]]
[[Category: Cousido-Siah, A]]
[[Category: Ruiz, F.X]]