4xzn - Revision history

OCA at 10:51, 10 January 2024

OCA — Wed, 10 Jan 2024 10:51:41 GMT

←Older revision		Revision as of 10:51, 10 January 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4xzn]] 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=4XZN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XZN FirstGlance]. <br>		<table><tr><td colspan='2'>[[4xzn]] 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=4XZN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XZN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</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]] 1.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></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=4xzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xzn OCA], [https://pdbe.org/4xzn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xzn RCSB], [https://www.ebi.ac.uk/pdbsum/4xzn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xzn 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=4xzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xzn OCA], [https://pdbe.org/4xzn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xzn RCSB], [https://www.ebi.ac.uk/pdbsum/4xzn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xzn ProSAT]</span></td></tr>
	</table>		</table>

OCA at 17:59, 26 April 2023

OCA — Wed, 26 Apr 2023 17:59:56 GMT

←Older revision		Revision as of 17:59, 26 April 2023
Line 3:		Line 3:
	<StructureSection load='4xzn' size='340' side='right'caption='[[4xzn]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='4xzn' size='340' side='right'caption='[[4xzn]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4xzn]] 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=4XZN OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4XZN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4xzn]] 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=4XZN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XZN FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene><~~/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=4xzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xzn OCA], [https://pdbe.org/4xzn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xzn RCSB], [https://www.ebi.ac.uk/pdbsum/4xzn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xzn ProSAT]</span></td></tr>
-	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b></td><td class="sblockDat">[[1zua\|1zua]]</td></tr>~~	+
-	~~<tr id='gene~~'>~~<td class="sblockLbl"><b>[[Gene\|Gene:]]~~</b>~~</td><td class="sblockDat">AKR1B10, AKR1B11 ([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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4xzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xzn OCA], [~~http~~://pdbe.org/4xzn PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4xzn RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4xzn PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4xzn ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/AK1BA_HUMAN AK1BA_HUMAN]] Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs.<ref>PMID:18087047</ref>	+	[https://www.uniprot.org/uniprot/AK1BA_HUMAN AK1BA_HUMAN] Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs.<ref>PMID:18087047</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Cousido-Siah, A]]	+	[[Category: Cousido-Siah A]]
-	[[Category: Mitschler, A]]	+	[[Category: Mitschler A]]
-	[[Category: Podjarny, A]]	+	[[Category: Podjarny A]]
-	[[Category: Ruiz~~, F X]]~~	+	[[Category: Ruiz FX]]
-	~~[[Category: Aldo-keto reductase 1b10]]~~	+
-	~~[[Category: Cytosolic]]~~	+
-	~~[[Category: Holoenzyme]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+
-	~~[[Category: Tim barrel~~]]	+

OCA at 00:27, 6 June 2019

OCA — Thu, 06 Jun 2019 00:27:44 GMT

←Older revision		Revision as of 00:27, 6 June 2019
Line 1:		Line 1:
		+
	==Crystal structure of the methylated K125R/V301L AKR1B10 Holoenzyme==		==Crystal structure of the methylated K125R/V301L AKR1B10 Holoenzyme==
-	<StructureSection load='4xzn' size='340' side='right' caption='[[4xzn]], [[Resolution\|resolution]] 1.70Å' scene=''>	+	<StructureSection load='4xzn' size='340' side='right'caption='[[4xzn]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4xzn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XZN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XZN FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4xzn]] 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=4XZN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XZN FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1zua\|1zua]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1zua\|1zua]]</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=4xzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xzn OCA], [http://pdbe.org/4xzn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xzn RCSB], [http://www.ebi.ac.uk/pdbsum/4xzn PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AKR1B10, AKR1B11 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xzn OCA], [http://pdbe.org/4xzn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xzn RCSB], [http://www.ebi.ac.uk/pdbsum/4xzn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xzn ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4xzn" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4xzn" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Aldo-keto reductase 3D structures\|Aldo-keto reductase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Cousido-Siah, A]]		[[Category: Cousido-Siah, A]]
	[[Category: Mitschler, A]]		[[Category: Mitschler, A]]

OCA at 18:57, 1 December 2015

OCA — Tue, 01 Dec 2015 18:57:14 GMT

←Older revision		Revision as of 18:57, 1 December 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of the methylated K125R/V301L AKR1B10 Holoenzyme==
		+	<StructureSection load='4xzn' size='340' side='right' caption='[[4xzn]], [[Resolution\|resolution]] 1.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4xzn]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XZN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XZN FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLY:N-DIMETHYL-LYSINE'>MLY</scene>, <scene name='pdbligand=MLZ:N-METHYL-LYSINE'>MLZ</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1zua\|1zua]]</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=4xzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xzn OCA], [http://pdbe.org/4xzn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xzn RCSB], [http://www.ebi.ac.uk/pdbsum/4xzn PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/AK1BA_HUMAN AK1BA_HUMAN]] Acts as all-trans-retinaldehyde reductase. Can efficiently reduce aliphatic and aromatic aldehydes, and is less active on hexoses (in vitro). May be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs.<ref>PMID:18087047</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The human enzymes aldose reductase (AR) and AKR1B10 have been thoroughly explored in terms of their roles in diabetes, inflammatory disorders, and cancer. In this study we identified two new lead compounds, 2-(3-(4-chloro-3-nitrobenzyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetic acid (JF0048, 3) and 2-(2,4-dioxo-3-(2,3,4,5-tetrabromo-6-methoxybenzyl)-3,4-dihydropyrimidin-1(2H)-yl )acetic acid (JF0049, 4), which selectively target these enzymes. Although 3 and 4 share the 3-benzyluracil-1-acetic acid scaffold, they have different substituents in their aryl moieties. Inhibition studies along with thermodynamic and structural characterizations of both enzymes revealed that the chloronitrobenzyl moiety of compound 3 can open the AR specificity pocket but not that of the AKR1B10 cognate. In contrast, the larger atoms at the ortho and/or meta positions of compound 4 prevent the AR specificity pocket from opening due to steric hindrance and provide a tighter fit to the AKR1B10 inhibitor binding pocket, probably enhanced by the displacement of a disordered water molecule trapped in a hydrophobic subpocket, creating an enthalpic signature. Furthermore, this selectivity also occurs in the cell, which enables the development of a more efficient drug design strategy: compound 3 prevents sorbitol accumulation in human retinal ARPE-19 cells, whereas 4 stops proliferation in human lung cancer NCI-H460 cells.

-	~~The entry 4xzn is ON HOLD until Paper Publication~~	+	Structural Determinants of the Selectivity of 3-Benzyluracil-1-acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10.,Ruiz FX, Cousido-Siah A, Porte S, Dominguez M, Crespo I, Rechlin C, Mitschler A, de Lera AR, Martin MJ, de la Fuente JA, Klebe G, Pares X, Farres J, Podjarny A ChemMedChem. 2015 Nov 9. doi: 10.1002/cmdc.201500393. PMID:26549844<ref>PMID:26549844</ref>

-	~~Authors: Cousido-Siah~~, A.~~, Ruiz, F~~.~~X., Mitschler, A., Podjarny, A~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Crystal structure of the methylated K125R~~/~~V301L AKR1B10 Holoenzyme~~	+	<div class="pdbe-citations 4xzn" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Unreleased Structures~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Cousido-Siah, A]]
		+	[[Category: Mitschler, A]]
	[[Category: Podjarny, A]]		[[Category: Podjarny, A]]
-	[[Category: ~~Mitschler~~, A]]	+	[[Category: Ruiz, F X]]
-	[[Category: ~~Cousido~~-~~Siah, A~~]]	+	[[Category: Aldo-keto reductase 1b10]]
-	[[Category: ~~Ruiz, F.X~~]]	+	[[Category: Cytosolic]]
		+	[[Category: Holoenzyme]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Tim barrel]]

OCA at 11:50, 18 February 2015

OCA — Wed, 18 Feb 2015 11:50:00 GMT

←Older revision		Revision as of 11:50, 18 February 2015
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4xzn is ON HOLD	+	The entry 4xzn is ON HOLD until Paper Publication

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

OCA: Protected "4xzn" [edit=sysop:move=sysop]

OCA — Thu, 12 Feb 2015 10:54:58 GMT

Protected "4xzn" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:54, 12 February 2015

OCA: New page: '''Unreleased structure''' The entry 4xzn is ON HOLD Authors: Cousido-Siah, A., Ruiz, F.X., Mitschler, A., Podjarny, A. Description: Crystal structure of the methylated K125R/V301L AKR...

OCA — Thu, 12 Feb 2015 10:54:56 GMT

New page: '''Unreleased structure''' The entry 4xzn is ON HOLD Authors: Cousido-Siah, A., Ruiz, F.X., Mitschler, A., Podjarny, A. Description: Crystal structure of the methylated K125R/V301L AKR...

New page

'''Unreleased structure'''

The entry 4xzn is ON HOLD

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

Description: Crystal structure of the methylated K125R/V301L AKR1B10 Holoenzyme
[[Category: Unreleased Structures]]
[[Category: Podjarny, A]]
[[Category: Mitschler, A]]
[[Category: Cousido-Siah, A]]
[[Category: Ruiz, F.X]]