6gxk - Revision history

OCA at 17:25, 20 November 2019

OCA — Wed, 20 Nov 2019 17:25:27 GMT

←Older revision		Revision as of 17:25, 20 November 2019
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	<StructureSection load='6gxk' size='340' side='right'caption='[[6gxk]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='6gxk' size='340' side='right'caption='[[6gxk]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6gxk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GXK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GXK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6gxk]] is a 2 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=6GXK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GXK 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=FFW:4-[[1-(4-chlorophenyl)carbonyl-5-methoxy-2-methyl-indol-3-yl]methyl]-1,2,5-oxadiazol-3-one'>FFW</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=FFW:4-[[1-(4-chlorophenyl)carbonyl-5-methoxy-2-methyl-indol-3-yl]methyl]-1,2,5-oxadiazol-3-one'>FFW</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">AKR1C3, DDH1, HSD17B5, KIAA0119, PGFS ([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=6gxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gxk OCA], [http://pdbe.org/6gxk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gxk RCSB], [http://www.ebi.ac.uk/pdbsum/6gxk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gxk 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=6gxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gxk OCA], [http://pdbe.org/6gxk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gxk RCSB], [http://www.ebi.ac.uk/pdbsum/6gxk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gxk ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/AK1C3_HUMAN AK1C3_HUMAN]] Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.		[[http://www.uniprot.org/uniprot/AK1C3_HUMAN AK1C3_HUMAN]] Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aldo-keto reductase 1C3 (AKR1C3) is an attractive target in drug design for its role in resistance to anticancer therapy. Several nonsteroidal anti-inflammatory drugs such as indomethacin are known to inhibit AKR1C3 in a nonselective manner because of COX-off target effects. Here we designed two indomethacin analogues by proposing a bioisosteric connection between the indomethacin carboxylic acid function and either hydroxyfurazan or hydroxy triazole rings. Both compounds were found to target AKR1C3 in a selective manner. In particular, hydroxyfurazan derivative is highly selective for AKR1C3 over the 1C2 isoform (up to 90-times more) and inactive on COX enzymes. High-resolution crystal structure of its complex with AKR1C3 shed light onto the binding mode of the new inhibitors. In cell-based assays (on colorectal and prostate cancer cells), the two indomethacin analogues showed higher potency than indomethacin. Therefore, these two AKR1C3 inhibitors can be used to provide further insight into the role of AKR1C3 in cancer.
		+
		+	Bioisosteres of Indomethacin as Inhibitors of Aldo-Keto Reductase 1C3.,Lolli ML, Carnovale IM, Pippione AC, Wahlgren WY, Bonanni D, Marini E, Zonari D, Gallicchio M, Boscaro V, Goyal P, Friemann R, Rolando B, Bagnati R, Adinolfi S, Oliaro-Bosso S, Boschi D ACS Med Chem Lett. 2019 Jan 28;10(4):437-443. doi:, 10.1021/acsmedchemlett.8b00484. eCollection 2019 Apr 11. PMID:30996776<ref>PMID:30996776</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6gxk" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Friemann, R]]		[[Category: Friemann, R]]

OCA at 11:18, 10 May 2019

OCA — Fri, 10 May 2019 11:18:11 GMT

←Older revision		Revision as of 11:18, 10 May 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6gxk is ~~ON HOLD~~	+	==Crystal structure of Aldo-Keto Reductase 1C3 (AKR1C3) complexed with inhibitor.==
-		+	<StructureSection load='6gxk' size='340' side='right'caption='[[6gxk]], [[Resolution\|resolution]] 1.70Å' scene=''>
-	~~Authors~~: ~~Goyal~~, P., ~~Wahlgren~~, W.Y., ~~Friemann~~, R.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6gxk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GXK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GXK FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of ~~Aldo-Keto Reductase 1C3~~ (~~AKR1C3~~) ~~complexed~~ with ~~inhibitor~~.	+	</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=FFW:4-[[1-(4-chlorophenyl)carbonyl-5-methoxy-2-methyl-indol-3-yl]methyl]-1,2,5-oxadiazol-3-one'>FFW</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6gxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gxk OCA], [http://pdbe.org/6gxk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gxk RCSB], [http://www.ebi.ac.uk/pdbsum/6gxk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gxk ProSAT]</span></td></tr>
-	[[Category: ~~Wahlgren~~, ~~W.Y~~]]	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/AK1C3_HUMAN AK1C3_HUMAN]] Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Friemann, R]]
	[[Category: Goyal, P]]		[[Category: Goyal, P]]
-	[[Category: ~~Friemann~~, R]]	+	[[Category: Wahlgren, W Y]]
		+	[[Category: Akr1c3]]
		+	[[Category: Aldo-keto reductase 1c3]]
		+	[[Category: Bioisosterism]]
		+	[[Category: Crpc]]
		+	[[Category: Inhibitor]]
		+	[[Category: Oxidoreductase]]
		+	[[Category: Prostate cancer]]
		+	[[Category: Scaffold hopping]]

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

OCA — Wed, 04 Jul 2018 05:57:09 GMT

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

←Older revision

Revision as of 05:57, 4 July 2018

OCA: New page: '''Unreleased structure''' The entry 6gxk is ON HOLD Authors: Goyal, P., Wahlgren, W.Y., Friemann, R. Description: Crystal structure of Aldo-Keto Reductase 1C3 (AKR1C3) complexed with ...

OCA — Wed, 04 Jul 2018 05:57:08 GMT

New page: '''Unreleased structure''' The entry 6gxk is ON HOLD Authors: Goyal, P., Wahlgren, W.Y., Friemann, R. Description: Crystal structure of Aldo-Keto Reductase 1C3 (AKR1C3) complexed with ...

New page

'''Unreleased structure'''

The entry 6gxk is ON HOLD

Authors: Goyal, P., Wahlgren, W.Y., Friemann, R.

Description: Crystal structure of Aldo-Keto Reductase 1C3 (AKR1C3) complexed with inhibitor.
[[Category: Unreleased Structures]]
[[Category: Wahlgren, W.Y]]
[[Category: Goyal, P]]
[[Category: Friemann, R]]