7c7h - Revision history

OCA at 15:58, 29 November 2023

OCA — Wed, 29 Nov 2023 15:58:26 GMT

←Older revision		Revision as of 15:58, 29 November 2023
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	<StructureSection load='7c7h' size='340' side='right'caption='[[7c7h]], [[Resolution\|resolution]] 1.86Å' scene=''>		<StructureSection load='7c7h' size='340' side='right'caption='[[7c7h]], [[Resolution\|resolution]] 1.86Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7c7h]] 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=7C7H OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7C7H FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7c7h]] is a 2 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=7C7H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C7H FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=FJU:2~~-~~azanylidene-N-(3-ethylphenyl)-8-oxidanyl-chromene-3-carboxamide'>FJU</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]] 1.86Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FJU:2-azanylidene-N-(3-ethylphenyl)-8-oxidanyl-chromene-3-carboxamide'>FJU</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
-	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Trans-1,~~2-~~dihydrobenzene~~-~~1,2~~-~~diol_dehydrogenase Trans~~-~~1,2~~-~~dihydrobenzene~~-~~1,2~~-~~diol dehydrogenase]~~, ~~with EC number [http~~:~~//www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=1.3.1.20 1.3.1.20]~~ </~~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=7c7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c7h OCA], [https://pdbe.org/7c7h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c7h RCSB], [https://www.ebi.ac.uk/pdbsum/7c7h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c7h ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7c7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c7h OCA], [~~http~~://pdbe.org/7c7h PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7c7h RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7c7h PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7c7h 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.	+	[https://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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7c7h" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7c7h" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Prostaglandin F synthase 3D structures\|Prostaglandin F synthase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase]]~~	+	[[Category: Endo S]]
-	[[Category: Endo, S]]	+	[[Category: Irie K]]
-	[[Category: Irie, K]]	+	[[Category: Toyooka N]]
-	[[Category: Toyooka, N]]	+
-	~~[[Category: Cancer]]~~	+
-	~~[[Category: Oxidoreductase~~]]	+

OCA at 06:43, 7 October 2020

OCA — Wed, 07 Oct 2020 06:43:12 GMT

←Older revision		Revision as of 06:43, 7 October 2020
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	==Crystal structures of AKR1C3 ternary complex with NADP+ and the chromene derivative 2l==		==Crystal structures of AKR1C3 ternary complex with NADP+ and the chromene derivative 2l==
-	<StructureSection load='7c7h' size='340' side='right'caption='[[7c7h]]' scene=''>	+	<StructureSection load='7c7h' size='340' side='right'caption='[[7c7h]], [[Resolution\|resolution]] 1.86Å' 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=7C7H OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7C7H FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7c7h]] 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=7C7H OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7C7H FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7c7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c7h OCA], [http://pdbe.org/7c7h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7c7h RCSB], [http://www.ebi.ac.uk/pdbsum/7c7h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7c7h 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=FJU:2-azanylidene-N-(3-ethylphenyl)-8-oxidanyl-chromene-3-carboxamide'>FJU</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trans-1,2-dihydrobenzene-1,2-diol_dehydrogenase Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.20 1.3.1.20] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7c7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c7h OCA], [http://pdbe.org/7c7h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7c7h RCSB], [http://www.ebi.ac.uk/pdbsum/7c7h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7c7h ProSAT]</span></td></tr>
	</table>		</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.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aldo-keto reductase (AKR) 1C3 catalyzes the synthesis of active androgens that promote the progression of prostate cancer. AKR1C3 also contributes to androgen-independent cell proliferation and survival through the metabolism of prostaglandins and reactive aldehydes. Because of its elevation in castration-resistant prostate cancer (CRPC) tissues, AKR1C3 is a promising therapeutic target for CRPC. In this study, we found a novel potent AKR1C3 inhibitor, N-(4-fluorophenyl)-8-hydroxy-2-imino-2H-chromene-3-carboxamide (2d), and synthesized its derivatives with IC50 values of 25-56 nM and >220-fold selectivity over other AKRs (1C1, 1C2, and 1C4). The structural factors for the inhibitory potency were elucidated by crystallographic study of AKR1C3 complexes with 2j and 2l. The inhibitors suppressed proliferation of prostate cancer 22Rv1 and PC3 cells through both androgen-dependent and androgen-independent mechanisms. Additionally, 2j and 2l prevented prostate tumor growth in a xenograft mouse model. Furthermore, the inhibitors significantly augmented apoptotic cell death induced by anti-CRPC drugs (abiraterone or enzalutamide).
		+
		+	Development of Novel AKR1C3 Inhibitors as New Potential Treatment for Castration-Resistant Prostate Cancer.,Endo S, Oguri H, Segawa J, Kawai M, Hu D, Xia S, Okada T, Irie K, Fujii S, Gouda H, Iguchi K, Matsukawa T, Fujimoto N, Nakayama T, Toyooka N, Matsunaga T, Ikari A J Med Chem. 2020 Sep 9. doi: 10.1021/acs.jmedchem.0c00939. PMID:32847363<ref>PMID:32847363</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7c7h" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Endo S]]	+	[[Category: Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase]]
-	[[Category: Irie K]]	+	[[Category: Endo, S]]
-	[[Category: Toyooka N]]	+	[[Category: Irie, K]]
		+	[[Category: Toyooka, N]]
		+	[[Category: Cancer]]
		+	[[Category: Oxidoreductase]]

OCA at 11:16, 23 September 2020

OCA — Wed, 23 Sep 2020 11:16:12 GMT

←Older revision		Revision as of 11:16, 23 September 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7c7h is ON HOLD until Paper Publication~~	+	==Crystal structures of AKR1C3 ternary complex with NADP+ and the chromene derivative 2l==
-		+	<StructureSection load='7c7h' size='340' side='right'caption='[[7c7h]]' scene=''>
-	~~Authors: Irie, K., Toyooka, N., Endo, S.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C7H OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7C7H FirstGlance]. <br>
-	~~Description:~~ Crystal structures of AKR1C3 ternary complex with NADP+ and the chromene derivative 2l	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7c7h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c7h OCA], [http://pdbe.org/7c7h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7c7h RCSB], [http://www.ebi.ac.uk/pdbsum/7c7h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7c7h ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Toyooka~~, N]]	+	__TOC__
-	[[Category: Endo, S]]	+	</StructureSection>
-	[[Category: Irie, K]]	+	[[Category: Large Structures]]
		+	[[Category: Endo S]]
		+	[[Category: Irie K]]
		+	[[Category: Toyooka N]]

OCA: Protected "7c7h" [edit=sysop:move=sysop]

OCA — Wed, 03 Jun 2020 05:27:18 GMT

Protected "7c7h" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:27, 3 June 2020

OCA: New page: '''Unreleased structure''' The entry 7c7h is ON HOLD until Paper Publication Authors: Irie, K., Toyooka, N., Endo, S. Description: Crystal structures of AKR1C3 ternary complex with NAD...

OCA — Wed, 03 Jun 2020 05:27:17 GMT

New page: '''Unreleased structure''' The entry 7c7h is ON HOLD until Paper Publication Authors: Irie, K., Toyooka, N., Endo, S. Description: Crystal structures of AKR1C3 ternary complex with NAD...

New page

'''Unreleased structure'''

The entry 7c7h is ON HOLD until Paper Publication

Authors: Irie, K., Toyooka, N., Endo, S.

Description: Crystal structures of AKR1C3 ternary complex with NADP+ and the chromene derivative 2l
[[Category: Unreleased Structures]]
[[Category: Toyooka, N]]
[[Category: Endo, S]]
[[Category: Irie, K]]