5o42 - Revision history

OCA at 19:07, 29 November 2023

OCA — Wed, 29 Nov 2023 19:07:37 GMT

←Older revision		Revision as of 19:07, 29 November 2023
Line 1:		Line 1:

	==17beta-hydroxysteroid dehydrogenase 14 variant T205 in complex with a non-steroidal 2,6-pyridinketone inhibitor.==		==17beta-hydroxysteroid dehydrogenase 14 variant T205 in complex with a non-steroidal 2,6-pyridinketone inhibitor.==
-	<StructureSection load='5o42' size='340' side='right' caption='[[5o42]], [[Resolution\|resolution]] 1.76Å' scene=''>	+	<StructureSection load='5o42' size='340' side='right'caption='[[5o42]], [[Resolution\|resolution]] 1.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5o42]] 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=5O42 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5O42 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5o42]] 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=5O42 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O42 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9JW:2-fluoranyl-3-[6-[1-(4-fluoranyl-3-oxidanyl-phenyl)ethenyl]pyridin-2-yl]phenol'>9JW</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]] 1.76Å</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=9JW:2-fluoranyl-3-[6-[1-(4-fluoranyl-3-oxidanyl-phenyl)ethenyl]pyridin-2-yl]phenol'>9JW</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=5o42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o42 OCA], [~~http~~://pdbe.org/5o42 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5o42 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5o42 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5o42 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=5o42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o42 OCA], [https://pdbe.org/5o42 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o42 RCSB], [https://www.ebi.ac.uk/pdbsum/5o42 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o42 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 ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5o42" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5o42" 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~~]]	+

OCA at 08:01, 14 June 2018

OCA — Thu, 14 Jun 2018 08:01:15 GMT

←Older revision		Revision as of 08:01, 14 June 2018
Line 3:		Line 3:
	<StructureSection load='5o42' size='340' side='right' caption='[[5o42]], [[Resolution\|resolution]] 1.76Å' scene=''>		<StructureSection load='5o42' size='340' side='right' caption='[[5o42]], [[Resolution\|resolution]] 1.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5o42]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O42 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O42 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5o42]] 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=5O42 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O42 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9JW:2-fluoranyl-3-[6-[1-(4-fluoranyl-3-oxidanyl-phenyl)ethenyl]pyridin-2-yl]phenol'>9JW</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=9JW:2-fluoranyl-3-[6-[1-(4-fluoranyl-3-oxidanyl-phenyl)ethenyl]pyridin-2-yl]phenol'>9JW</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=5o42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o42 OCA], [http://pdbe.org/5o42 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o42 RCSB], [http://www.ebi.ac.uk/pdbsum/5o42 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o42 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=5o42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o42 OCA], [http://pdbe.org/5o42 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o42 RCSB], [http://www.ebi.ac.uk/pdbsum/5o42 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o42 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 5o42" 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 05:47, 6 June 2018

OCA — Wed, 06 Jun 2018 05:47:41 GMT

←Older revision		Revision as of 05:47, 6 June 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5o42 ~~is ON HOLD until Paper Publication~~	+	==17beta-hydroxysteroid dehydrogenase 14 variant T205 in complex with a non-steroidal 2,6-pyridinketone inhibitor.==
-		+	<StructureSection load='5o42' size='340' side='right' caption='[[5o42]], [[Resolution\|resolution]] 1.76Å' scene=''>
-	~~Authors~~: ~~Bertoletti, N~~., ~~Heine~~, A., ~~Braun~~, F., ~~Klebe~~, G., ~~Marchais~~-~~Oberwinkler, S~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5o42]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O42 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O42 FirstGlance]. <br>
-	~~Description~~: ~~17beta~~-hydroxysteroid dehydrogenase ~~14 variant T205 in complex with a non~~-~~steroidal 2~~,6-~~pyridinketone inhibitor~~.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9JW:2-fluoranyl-3-[6-[1-(4-fluoranyl-3-oxidanyl-phenyl)ethenyl]pyridin-2-yl]phenol'>9JW</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=5o42 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o42 OCA], [http://pdbe.org/5o42 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o42 RCSB], [http://www.ebi.ac.uk/pdbsum/5o42 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o42 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]]

OCA: Protected "5o42" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 12:01:23 GMT

Protected "5o42" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:01, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5o42 is ON HOLD until Paper Publication Authors: Bertoletti, N., Heine, A., Braun, F., Klebe, G., Marchais-Oberwinkler, S. Description: 17beta-hydr...

OCA — Wed, 27 Sep 2017 12:01:21 GMT

New page: '''Unreleased structure''' The entry 5o42 is ON HOLD until Paper Publication Authors: Bertoletti, N., Heine, A., Braun, F., Klebe, G., Marchais-Oberwinkler, S. Description: 17beta-hydr...

New page

'''Unreleased structure'''

The entry 5o42 is ON HOLD until Paper Publication

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

Description: 17beta-hydroxysteroid dehydrogenase 14 variant T205 in complex with a non-steroidal 2,6-pyridinketone inhibitor.
[[Category: Unreleased Structures]]
[[Category: Heine, A]]
[[Category: Braun, F]]
[[Category: Bertoletti, N]]
[[Category: Marchais-Oberwinkler, S]]
[[Category: Klebe, G]]