5o7c - Revision history

OCA at 19:10, 29 November 2023

2023-11-29T19:10:23Z

← Older revision		Revision as of 19:10, 29 November 2023
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	==17beta-hydroxysteroid dehydrogenase 14 variant T205 in complex with a non-steroidal quinoline based inhibitor==		==17beta-hydroxysteroid dehydrogenase 14 variant T205 in complex with a non-steroidal quinoline based inhibitor==
	<StructureSection load='5o7c' size='340' side='right' caption='[[5o7c]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='5o7c' size='340' side='right'caption='[[5o7c]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5o7c]] 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=5O7C OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5O7C FirstGlance]. <br>		<table><tr><td colspan='2'>[[5o7c]] 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=5O7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O7C FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9N2:2-(4-fluoranyl-3-oxidanyl-phenyl)carbonylquinoline-7-carbonitrile'>9N2</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 1.6Å</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HSD17B14, DHRS10, SDR3, SDR47C1, UNQ502/PRO474 ([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=9N2:2-(4-fluoranyl-3-oxidanyl-phenyl)carbonylquinoline-7-carbonitrile'>9N2</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></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=5o7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o7c OCA], [~~http~~://pdbe.org/5o7c PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5o7c RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5o7c PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5o7c 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=5o7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o7c OCA], [https://pdbe.org/5o7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o7c RCSB], [https://www.ebi.ac.uk/pdbsum/5o7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o7c ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/DHB14_HUMAN DHB14_HUMAN]] Has NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity. Converts oestradiol to oestrone. The physiological substrate is not known. Acts on oestradiol and 5-androstene-3-beta,17-beta-diol (in vitro).<ref>PMID:17067289</ref>		[https://www.uniprot.org/uniprot/DHB14_HUMAN DHB14_HUMAN] Has NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity. Converts oestradiol to oestrone. The physiological substrate is not known. Acts on oestradiol and 5-androstene-3-beta,17-beta-diol (in vitro).<ref>PMID:17067289</ref>
	<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 5o7c" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5o7c" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Hydroxysteroid dehydrogenase 3D structures\|Hydroxysteroid dehydrogenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Bertoletti, N]]		[[Category: Large Structures]]
	[[Category: Braun, F]]		[[Category: Bertoletti N]]
	[[Category: Heine, A]]		[[Category: Braun F]]
	[[Category: Klebe, G]]		[[Category: Heine A]]
	[[Category: Marchais-Oberwinkler, S]]		[[Category: Klebe G]]
	~~[[Category: 17beta-hsd14]]~~		[[Category: Marchais-Oberwinkler S]]
	~~[[Category: Non-steroidal inhibitor]]~~
	~~[[Category: Oxidoreductase]]~~
	~~[[Category: Quinoline based inhibitor~~]]

OCA at 08:01, 14 June 2018

2018-06-14T08:01:43Z

← Older revision		Revision as of 08:01, 14 June 2018
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	<StructureSection load='5o7c' size='340' side='right' caption='[[5o7c]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='5o7c' size='340' side='right' caption='[[5o7c]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5o7c]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O7C FirstGlance]. <br>		<table><tr><td colspan='2'>[[5o7c]] 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=5O7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O7C FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9N2:2-(4-fluoranyl-3-oxidanyl-phenyl)carbonylquinoline-7-carbonitrile'>9N2</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9N2:2-(4-fluoranyl-3-oxidanyl-phenyl)carbonylquinoline-7-carbonitrile'>9N2</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HSD17B14, DHRS10, SDR3, SDR47C1, UNQ502/PRO474 ([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=5o7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o7c OCA], [http://pdbe.org/5o7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o7c RCSB], [http://www.ebi.ac.uk/pdbsum/5o7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o7c 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=5o7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o7c OCA], [http://pdbe.org/5o7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o7c RCSB], [http://www.ebi.ac.uk/pdbsum/5o7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o7c ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/DHB14_HUMAN DHB14_HUMAN]] Has NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity. Converts oestradiol to oestrone. The physiological substrate is not known. Acts on oestradiol and 5-androstene-3-beta,17-beta-diol (in vitro).<ref>PMID:17067289</ref>		[[http://www.uniprot.org/uniprot/DHB14_HUMAN DHB14_HUMAN]] Has NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity. Converts oestradiol to oestrone. The physiological substrate is not known. Acts on oestradiol and 5-androstene-3-beta,17-beta-diol (in vitro).<ref>PMID:17067289</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The human enzyme 17beta-hydroxysteroid dehydrogenase 14 (17beta-HSD14) oxidizes the hydroxyl group at position 17 of estradiol and 5-androstenediol using NAD(+) as cofactor. However, the physiological role of the enzyme remains unclear. We recently described the first class of nonsteroidal inhibitors for this enzyme with compound 1 showing a high 17beta-HSD14 inhibitory activity. Its crystal structure was used as starting point for a structure-based optimization in this study. The goal was to develop a promising chemical probe to further investigate the enzyme. The newly designed compounds revealed mostly very high inhibition of the enzyme and for seven of them the crystal structures of the corresponding inhibitor-enzyme complexes were resolved. The crystal structures disclosed that a small change in the substitution pattern of the compounds resulted in an alternative binding mode for one inhibitor. The profiling of a set of the most potent inhibitors identified 13 (Ki=9nM) with a good selectivity profile toward three 17beta-HSDs and the estrogen receptor alpha. This inhibitor displayed no cytotoxicity, good solubility, and auspicious predicted bioavailability. Overall, 13 is a highly interesting 17beta-HSD14 inhibitor, which might be used as chemical probe for further investigation of the target enzyme.

			Structure-based design and profiling of novel 17beta-HSD14 inhibitors.,Braun F, Bertoletti N, Moller G, Adamski J, Frotscher M, Guragossian N, Madeira Girio PA, Le Borgne M, Ettouati L, Falson P, Muller S, Vollmer G, Heine A, Klebe G, Marchais-Oberwinkler S Eur J Med Chem. 2018 May 22;155:61-76. doi: 10.1016/j.ejmech.2018.05.029. PMID:29859505<ref>PMID:29859505</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 5o7c" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
	[[Category: Bertoletti, N]]		[[Category: Bertoletti, N]]
	[[Category: Braun, F]]		[[Category: Braun, F]]

OCA at 05:48, 6 June 2018

2018-06-06T05:48:07Z

← Older revision		Revision as of 05:48, 6 June 2018
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 5o7c is ~~ON HOLD until Paper Publication~~		==17beta-hydroxysteroid dehydrogenase 14 variant T205 in complex with a non-steroidal quinoline based inhibitor==
			<StructureSection load='5o7c' size='340' side='right' caption='[[5o7c]], [[Resolution\|resolution]] 1.60Å' scene=''>
	~~Authors~~: ~~Bertoletti~~, N., ~~Braun~~, F., ~~Heine~~, A., ~~Klebe~~, G., ~~Marchais~~-~~Oberwinkler, S~~.		== Structural highlights ==
			<table><tr><td colspan='2'>[[5o7c]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O7C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O7C FirstGlance]. <br>
	~~Description~~: ~~17beta~~-hydroxysteroid dehydrogenase ~~14 variant T205~~ in ~~complex with a non-steroidal quinoline based inhibitor~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9N2:2-(4-fluoranyl-3-oxidanyl-phenyl)carbonylquinoline-7-carbonitrile'>9N2</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=5o7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o7c OCA], [http://pdbe.org/5o7c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o7c RCSB], [http://www.ebi.ac.uk/pdbsum/5o7c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o7c ProSAT]</span></td></tr>
			</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/DHB14_HUMAN DHB14_HUMAN]] Has NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity. Converts oestradiol to oestrone. The physiological substrate is not known. Acts on oestradiol and 5-androstene-3-beta,17-beta-diol (in vitro).<ref>PMID:17067289</ref>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Bertoletti, N]]
			[[Category: Braun, F]]
	[[Category: Heine, A]]		[[Category: Heine, A]]
	[[Category: ~~Braun~~, ~~F]]~~		[[Category: Klebe, G]]
	~~[[Category: Bertoletti, N~~]]
	[[Category: Marchais-Oberwinkler, S]]		[[Category: Marchais-Oberwinkler, S]]
	[[Category: ~~Klebe, G~~]]		[[Category: 17beta-hsd14]]
			[[Category: Non-steroidal inhibitor]]
			[[Category: Oxidoreductase]]
			[[Category: Quinoline based inhibitor]]

OCA: Protected "5o7c" [edit=sysop:move=sysop]

2017-09-27T12:06:41Z

Protected "5o7c" [edit=sysop:move=sysop]

← Older revision	Revision as of 12:06, 27 September 2017
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5o7c is ON HOLD until Paper Publication Authors: Bertoletti, N., Braun, F., Heine, A., Klebe, G., Marchais-Oberwinkler, S. Description: 17beta-hydr...

2017-09-27T12:06:40Z

New page: '''Unreleased structure''' The entry 5o7c is ON HOLD until Paper Publication Authors: Bertoletti, N., Braun, F., Heine, A., Klebe, G., Marchais-Oberwinkler, S. Description: 17beta-hydr...

New page

'''Unreleased structure'''

The entry 5o7c is ON HOLD until Paper Publication

Authors: Bertoletti, N., Braun, F., Heine, A., Klebe, G., Marchais-Oberwinkler, S.

Description: 17beta-hydroxysteroid dehydrogenase 14 variant T205 in complex with a non-steroidal quinoline based inhibitor
[[Category: Unreleased Structures]]
[[Category: Heine, A]]
[[Category: Braun, F]]
[[Category: Bertoletti, N]]
[[Category: Marchais-Oberwinkler, S]]
[[Category: Klebe, G]]