3klm - Revision history

OCA at 10:17, 21 February 2024

2024-02-21T10:17:24Z

← Older revision		Revision as of 10:17, 21 February 2024
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	<StructureSection load='3klm' size='340' side='right'caption='[[3klm]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='3klm' size='340' side='right'caption='[[3klm]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3klm]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=3KLM FirstGlance]. <br>		<table><tr><td colspan='2'>[[3klm]] 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=3KLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KLM FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=DHT:5-ALPHA~~-~~DIHYDROTESTOSTERONE'>DHT</scene>~~, ~~<scene name='pdbligand=GOL:GLYCEROL'>GOL</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='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks~~'>~~[http:~~/~~/en.wikipedia.org/wiki/17-beta-estradiol_17-dehydrogenase 17-beta-estradiol 17-dehydrogenase]~~, ~~with EC number [http~~:~~//www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62]~~ </~~span~~></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=3klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klm OCA], [~~http~~://pdbe.org/3klm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3klm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3klm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3klm 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=3klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klm OCA], [https://pdbe.org/3klm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3klm RCSB], [https://www.ebi.ac.uk/pdbsum/3klm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3klm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/DHB1_HUMAN DHB1_HUMAN]] Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.		[https://www.uniprot.org/uniprot/DHB1_HUMAN DHB1_HUMAN] Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 20:		Line 20:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3klm ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3klm ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	The active estrogen estradiol (E2) stimulates breast cancer cell (BCC) growth, whereas the androgen dihydrotestosterone (DHT) has shown an antiproliferative effect. The principal product synthesized by the 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is E2, although we have demonstrated that the purified enzyme also inactivates DHT. However, the direct roles of 17beta-HSD1 in sex-hormone regulation and BCC proliferation have not been completely established. Here, we show that 17beta-HSD1 inhibition suppresses DHT catabolism by 19%, whereas knockdown of the gene expression increases the concentration of DHT by 41% in the T47D BCC line. The 17beta-HSD1/DHT complex crystal structure reveals that DHT binds in both normal and reverse modes, but the latter mode leading to O3 reduction is preferred with stronger interactions. Using RNA interference and an inhibitor of 17beta-HSD1, we demonstrate that 17beta-HSD1 expression is negatively correlated to DHT levels in BCC but positively correlated to estrone reduction, E2 levels, and cell proliferation. 17beta-HSD1 inhibition reduces DHT inactivation, increasing the antiproliferative effect by DHT in T47D cells after 8 d treatment. Thus, 17beta-HSD1 up-regulates BCC growth by a dual action on estradiol synthesis and DHT inactivation. We have further demonstrated that 17beta-HSD1 can enhance the E2-induced expression of the endogenous estrogen-responsive gene pS2, providing an important information regarding the modulation of the estrogen responsiveness by 17beta-HSD1 that may also contribute to BCC growth. These results strongly support the rationale for inhibiting 17beta-HSD1 in breast cancer therapy to eliminate estrogen activation via the sulfatase pathway while avoiding the deprivation of DHT.

	17beta-hydroxysteroid dehydrogenase type 1 stimulates breast cancer by dihydrotestosterone inactivation in addition to estradiol production.,Aka JA, Mazumdar M, Chen CQ, Poirier D, Lin SX Mol Endocrinol. 2010 Apr;24(4):832-45. Epub 2010 Feb 19. PMID:20172961<ref>PMID:20172961</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 3klm" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Hydroxysteroid dehydrogenase 3D structures\|Hydroxysteroid dehydrogenase 3D structures]]		*[[Hydroxysteroid dehydrogenase 3D structures\|Hydroxysteroid dehydrogenase 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: 17-beta-estradiol 17-dehydrogenase]]~~
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Mazumdar, M]]		[[Category: Mazumdar M]]
	~~[[Category: Dht]]~~
	~~[[Category: Lipid synthesis]]~~
	~~[[Category: Oxidoreductase]]~~
	~~[[Category: Steroid biosynthesis~~]]

OCA at 07:02, 7 October 2020

2020-10-07T07:02:30Z

← Older revision		Revision as of 07:02, 7 October 2020
Line 1:		Line 1:

	==17beta-HSD1 in complex with DHT==		==17beta-HSD1 in complex with DHT==
	<StructureSection load='3klm' size='340' side='right' caption='[[3klm]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='3klm' size='340' side='right'caption='[[3klm]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3klm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3KLM FirstGlance]. <br>		<table><tr><td colspan='2'>[[3klm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3KLM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/17-beta-estradiol_17-dehydrogenase 17-beta-estradiol 17-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/17-beta-estradiol_17-dehydrogenase 17-beta-estradiol 17-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </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=3klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klm OCA], [http://pdbe.org/3klm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3klm RCSB], [http://www.ebi.ac.uk/pdbsum/3klm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3klm 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=3klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klm OCA], [http://pdbe.org/3klm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3klm RCSB], [http://www.ebi.ac.uk/pdbsum/3klm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3klm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 31:		Line 31:

	==See Also==		==See Also==
	*[[Hydroxysteroid dehydrogenase\|Hydroxysteroid dehydrogenase]]		*[[Hydroxysteroid dehydrogenase 3D structures\|Hydroxysteroid dehydrogenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 38:		Line 38:
	[[Category: 17-beta-estradiol 17-dehydrogenase]]		[[Category: 17-beta-estradiol 17-dehydrogenase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
			[[Category: Large Structures]]
	[[Category: Mazumdar, M]]		[[Category: Mazumdar, M]]
	[[Category: Dht]]		[[Category: Dht]]

OCA at 08:53, 26 December 2018

2018-12-26T08:53:14Z

← Older revision		Revision as of 08:53, 26 December 2018
Line 14:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kl/3klm_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kl/3klm_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>

OCA at 19:31, 5 August 2016

2016-08-05T19:31:20Z

← Older revision		Revision as of 19:31, 5 August 2016
Line 1:		Line 1:

	==17beta-HSD1 in complex with DHT==		==17beta-HSD1 in complex with DHT==
	<StructureSection load='3klm' size='340' side='right' caption='[[3klm]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='3klm' size='340' side='right' caption='[[3klm]], [[Resolution\|resolution]] 1.70Å' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[3klm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KLM FirstGlance]. <br>		<table><tr><td colspan='2'>[[3klm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KLM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/~~Estradiol_17~~-beta-dehydrogenase ~~Estradiol~~ 17-beta-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/17-beta-estradiol_17-dehydrogenase 17-beta-estradiol 17-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </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=3klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3klm RCSB], [http://www.ebi.ac.uk/pdbsum/3klm PDBsum]</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=3klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klm OCA], [http://pdbe.org/3klm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3klm RCSB], [http://www.ebi.ac.uk/pdbsum/3klm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3klm ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 18:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3klm ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 27:		Line 28:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 3klm" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 34:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Estradiol~~ 17-beta-dehydrogenase]]		[[Category: 17-beta-estradiol 17-dehydrogenase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mazumdar, M]]		[[Category: Mazumdar, M]]

OCA at 21:19, 25 December 2014

2014-12-25T21:19:58Z

← Older revision		Revision as of 21:19, 25 December 2014
Line 7:		Line 7:
	<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=3klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3klm RCSB], [http://www.ebi.ac.uk/pdbsum/3klm PDBsum]</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=3klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3klm RCSB], [http://www.ebi.ac.uk/pdbsum/3klm PDBsum]</span></td></tr>
	</table>		</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/DHB1_HUMAN DHB1_HUMAN]] Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 08:23, 9 December 2014

2014-12-09T08:23:39Z

← Older revision		Revision as of 08:23, 9 December 2014
Line 1:		Line 1:
	[[Image:~~3klm~~.~~png~~\|~~left~~\|~~200px~~]]		==17beta-HSD1 in complex with DHT==
			<StructureSection load='3klm' size='340' side='right' caption='[[3klm]], [[Resolution\|resolution]] 1.70Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[3klm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KLM FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Estradiol_17-beta-dehydrogenase Estradiol 17-beta-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] </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=3klm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3klm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3klm RCSB], [http://www.ebi.ac.uk/pdbsum/3klm PDBsum]</span></td></tr>
			</table>
			== Evolutionary Conservation ==
			[[Image:Consurf_key_small.gif\|200px\|right]]
			Check<jmol>
			<jmolCheckbox>
			<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kl/3klm_consurf.spt"</scriptWhenChecked>
			<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
			<text>to colour the structure by Evolutionary Conservation</text>
			</jmolCheckbox>
			</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The active estrogen estradiol (E2) stimulates breast cancer cell (BCC) growth, whereas the androgen dihydrotestosterone (DHT) has shown an antiproliferative effect. The principal product synthesized by the 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is E2, although we have demonstrated that the purified enzyme also inactivates DHT. However, the direct roles of 17beta-HSD1 in sex-hormone regulation and BCC proliferation have not been completely established. Here, we show that 17beta-HSD1 inhibition suppresses DHT catabolism by 19%, whereas knockdown of the gene expression increases the concentration of DHT by 41% in the T47D BCC line. The 17beta-HSD1/DHT complex crystal structure reveals that DHT binds in both normal and reverse modes, but the latter mode leading to O3 reduction is preferred with stronger interactions. Using RNA interference and an inhibitor of 17beta-HSD1, we demonstrate that 17beta-HSD1 expression is negatively correlated to DHT levels in BCC but positively correlated to estrone reduction, E2 levels, and cell proliferation. 17beta-HSD1 inhibition reduces DHT inactivation, increasing the antiproliferative effect by DHT in T47D cells after 8 d treatment. Thus, 17beta-HSD1 up-regulates BCC growth by a dual action on estradiol synthesis and DHT inactivation. We have further demonstrated that 17beta-HSD1 can enhance the E2-induced expression of the endogenous estrogen-responsive gene pS2, providing an important information regarding the modulation of the estrogen responsiveness by 17beta-HSD1 that may also contribute to BCC growth. These results strongly support the rationale for inhibiting 17beta-HSD1 in breast cancer therapy to eliminate estrogen activation via the sulfatase pathway while avoiding the deprivation of DHT.

	~~{{STRUCTURE_3klm\| PDB=3klm \| SCENE= }}~~		17beta-hydroxysteroid dehydrogenase type 1 stimulates breast cancer by dihydrotestosterone inactivation in addition to estradiol production.,Aka JA, Mazumdar M, Chen CQ, Poirier D, Lin SX Mol Endocrinol. 2010 Apr;24(4):832-45. Epub 2010 Feb 19. PMID:20172961<ref>PMID:20172961</ref>

	~~===17beta-HSD1 in complex with DHT===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~{{ABSTRACT_PUBMED_20172961}}~~

	~~==About this Structure==~~
	~~[[3klm]] is~~ a ~~1 chain structure with sequence from [http://en.wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann.ac.il/oca-bin~~/~~ocashort?id=3KLM OCA].~~

	==See Also==		==See Also==
	*[[Hydroxysteroid dehydrogenase\|Hydroxysteroid dehydrogenase]]		*[[Hydroxysteroid dehydrogenase\|Hydroxysteroid dehydrogenase]]
			== References ==
	==~~Reference~~==		<references/>
	<~~ref group="xtra">PMID:020172961<~~/~~ref~~><~~references group="xtra"~~/>		__TOC__
			</StructureSection>
	[[Category: Estradiol 17-beta-dehydrogenase]]		[[Category: Estradiol 17-beta-dehydrogenase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Mazumdar, M.]]		[[Category: Mazumdar, M]]
	[[Category: Dht]]		[[Category: Dht]]
	[[Category: Lipid synthesis]]		[[Category: Lipid synthesis]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
	[[Category: Steroid biosynthesis]]		[[Category: Steroid biosynthesis]]

OCA at 21:47, 20 October 2012

2012-10-20T21:47:42Z

← Older revision		Revision as of 21:47, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[3klm]] is a 1 chain structure ~~of [[Hydroxysteroid dehydrogenase]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA].		[[3klm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA].

	==See Also==		==See Also==

OCA at 14:18, 27 July 2012

2012-07-27T14:18:39Z

← Older revision		Revision as of 14:18, 27 July 2012
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	[[Image:3klm.png\|left\|200px]]		[[Image:3klm.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3klm", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_3klm\| PDB=3klm \| SCENE= }}		{{STRUCTURE_3klm\| PDB=3klm \| SCENE= }}

	===17beta-HSD1 in complex with DHT===		===17beta-HSD1 in complex with DHT===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_20172961}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 20172961 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_20172961}}		{{ABSTRACT_PUBMED_20172961}}

	==About this Structure==		==About this Structure==
	[[3klm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA].		[[3klm]] is a 1 chain structure of [[Hydroxysteroid dehydrogenase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA].

			==See Also==
			*[[Hydroxysteroid dehydrogenase\|Hydroxysteroid dehydrogenase]]

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~20172961~~</ref><references group="xtra"/>		<ref group="xtra">PMID:020172961</ref><references group="xtra"/>
	[[Category: Estradiol 17-beta-dehydrogenase]]		[[Category: Estradiol 17-beta-dehydrogenase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA: Protected "3klm" [edit=sysop:move=sysop]

2011-01-02T03:11:31Z

Protected "3klm" [edit=sysop:move=sysop]

← Older revision	Revision as of 03:11, 2 January 2011
(No difference)

OCA at 03:11, 2 January 2011

2011-01-02T03:11:30Z

← Older revision		Revision as of 03:11, 2 January 2011
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	~~{{Seed}}~~		[[Image:3klm.png\|left\|200px]]
	[[Image:3klm.~~jpg~~\|left\|200px]]

	<!--		<!--
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	==About this Structure==		==About this Structure==
	~~3KLM~~ is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA].		[[3klm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KLM OCA].

	==Reference==		==Reference==
Line 31:		Line 30:
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]
	[[Category: Steroid biosynthesis]]		[[Category: Steroid biosynthesis]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 21 09:56:52 2010''~~