2aa2 - Revision history

OCA at 08:07, 4 March 2026

2026-03-04T08:07:40Z

← Older revision		Revision as of 08:07, 4 March 2026
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	<StructureSection load='2aa2' size='340' side='right'caption='[[2aa2]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='2aa2' size='340' side='right'caption='[[2aa2]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[2aa2]] 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=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>
	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.95Å</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]] 1.95Å</td></tr>
	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [https://pdbe.org/2aa2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [https://www.ebi.ac.uk/pdbsum/2aa2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aa2 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=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [https://pdbe.org/2aa2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [https://www.ebi.ac.uk/pdbsum/2aa2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aa2 ProSAT]</span></td></tr>
	</table>		</table>
	~~== Disease ==~~
	[https://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[https://omim.org/entry/177735 177735]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.<ref>PMID:9662404</ref> <ref>PMID:11134129</ref> <ref>PMID:12788847</ref> <ref>PMID:16954160</ref> <ref>PMID:16972228</ref> Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:[https://omim.org/entry/605115 605115]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.<ref>PMID:9662404</ref> <ref>PMID:15967794</ref> <ref>PMID:15908963</ref> <ref>PMID:10884226</ref>
	~~== Function ==~~
	[https://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN] Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.<ref>PMID:3037703</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 17:		Line 13:
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/aa/2aa2_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/aa/2aa2_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/~~initialview01~~.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
	<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/main_output.php?pdb_ID=2aa2 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=2aa2 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand. In addition, most activating ligands hydrogen bond to Thr945 on helix 10. Structural characterization of the naturally occurring S810L mutant explains how stabilization of a helix 3/helix 5 interaction can circumvent the requirement for this hydrogen bond network. Taken together, these results explain the potency of MR activation by aldosterone, the weak activation induced by progesterone and the antihypertensive agent spironolactone, and the binding selectivity of cortisol over cortisone.

			A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor.,Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SP J Biol Chem. 2005 Sep 2;280(35):31283-93. Epub 2005 Jun 20. PMID:15967794<ref>PMID:15967794</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 2aa2" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 29:		Line 34:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	~~[[Category: Homo sapiens]]~~
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Apolito CJ]]		[[Category: Apolito CJ]]

OCA at 09:11, 14 February 2024

2024-02-14T09:11:59Z

← Older revision		Revision as of 09:11, 14 February 2024
Line 3:		Line 3:
	<StructureSection load='2aa2' size='340' side='right'caption='[[2aa2]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='2aa2' size='340' side='right'caption='[[2aa2]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2aa2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2aa2]] 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=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.95Å</td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2aa5\|2aa5]], [[2aa6\|2aa6]], [[2aa7\|2aa7]]</div></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR3C2, MCR, MLR ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [https://pdbe.org/2aa2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [https://www.ebi.ac.uk/pdbsum/2aa2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aa2 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=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [https://pdbe.org/2aa2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [https://www.ebi.ac.uk/pdbsum/2aa2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aa2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[https://omim.org/entry/177735 177735]]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.<ref>PMID:9662404</ref> <ref>PMID:11134129</ref> <ref>PMID:12788847</ref> <ref>PMID:16954160</ref> <ref>PMID:16972228</ref> Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:[https://omim.org/entry/605115 605115]]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.<ref>PMID:9662404</ref> <ref>PMID:15967794</ref> <ref>PMID:15908963</ref> <ref>PMID:10884226</ref>		[https://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[https://omim.org/entry/177735 177735]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.<ref>PMID:9662404</ref> <ref>PMID:11134129</ref> <ref>PMID:12788847</ref> <ref>PMID:16954160</ref> <ref>PMID:16972228</ref> Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:[https://omim.org/entry/605115 605115]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.<ref>PMID:9662404</ref> <ref>PMID:15967794</ref> <ref>PMID:15908963</ref> <ref>PMID:10884226</ref>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.<ref>PMID:3037703</ref>		[https://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN] Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.<ref>PMID:3037703</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 23:		Line 22:
	</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=2aa2 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=2aa2 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand. In addition, most activating ligands hydrogen bond to Thr945 on helix 10. Structural characterization of the naturally occurring S810L mutant explains how stabilization of a helix 3/helix 5 interaction can circumvent the requirement for this hydrogen bond network. Taken together, these results explain the potency of MR activation by aldosterone, the weak activation induced by progesterone and the antihypertensive agent spironolactone, and the binding selectivity of cortisol over cortisone.

	A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor.,Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SP J Biol Chem. 2005 Sep 2;280(35):31283-93. Epub 2005 Jun 20. PMID:15967794<ref>PMID:15967794</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 2aa2" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
Line 39:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Apolito~~, C J~~]]		[[Category: Apolito CJ]]
	[[Category: Bledsoe~~, R K~~]]		[[Category: Bledsoe RK]]
	[[Category: Holt~~, J A~~]]		[[Category: Holt JA]]
	[[Category: Lambert~~, M H~~]]		[[Category: Lambert MH]]
	[[Category: Madauss~~, K P~~]]		[[Category: Madauss KP]]
	[[Category: Pearce~~, K H~~]]		[[Category: Pearce KH]]
	[[Category: Stanley~~, T B~~]]		[[Category: Stanley TB]]
	[[Category: Stewart~~, E L~~]]		[[Category: Stewart EL]]
	[[Category: Trump~~, R P~~]]		[[Category: Trump RP]]
	[[Category: Williams~~, S P~~]]		[[Category: Williams SP]]
	[[Category: Willson~~, T M]]~~		[[Category: Willson TM]]
	~~[[Category: Aldosterone]]~~
	~~[[Category: Mineralocorticoid]]~~
	~~[[Category: Mr]]~~
	~~[[Category: Nuclear receptor]]~~
	~~[[Category: Steroid receptor]]~~
	~~[[Category: Transcription~~]]

OCA at 17:07, 20 October 2021

2021-10-20T17:07:58Z

← Older revision		Revision as of 17:07, 20 October 2021
Line 1:		Line 1:

	==Mineralocorticoid Receptor with Bound Aldosterone==		==Mineralocorticoid Receptor with Bound Aldosterone==
	<StructureSection load='2aa2' size='340' side='right'caption='[[2aa2]]' scene=''>		<StructureSection load='2aa2' size='340' side='right'caption='[[2aa2]], [[Resolution\|resolution]] 1.95Å' 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=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2aa2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>
	</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=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [https://pdbe.org/2aa2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [https://www.ebi.ac.uk/pdbsum/2aa2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aa2 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=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2aa5\|2aa5]], [[2aa6\|2aa6]], [[2aa7\|2aa7]]</div></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR3C2, MCR, MLR ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [https://pdbe.org/2aa2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [https://www.ebi.ac.uk/pdbsum/2aa2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aa2 ProSAT]</span></td></tr>
	</table>		</table>
			== Disease ==
			[[https://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[https://omim.org/entry/177735 177735]]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.<ref>PMID:9662404</ref> <ref>PMID:11134129</ref> <ref>PMID:12788847</ref> <ref>PMID:16954160</ref> <ref>PMID:16972228</ref> Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:[https://omim.org/entry/605115 605115]]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.<ref>PMID:9662404</ref> <ref>PMID:15967794</ref> <ref>PMID:15908963</ref> <ref>PMID:10884226</ref>
			== Function ==
			[[https://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.<ref>PMID:3037703</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 16:		Line 23:
	</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=2aa2 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=2aa2 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand. In addition, most activating ligands hydrogen bond to Thr945 on helix 10. Structural characterization of the naturally occurring S810L mutant explains how stabilization of a helix 3/helix 5 interaction can circumvent the requirement for this hydrogen bond network. Taken together, these results explain the potency of MR activation by aldosterone, the weak activation induced by progesterone and the antihypertensive agent spironolactone, and the binding selectivity of cortisol over cortisone.

			A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor.,Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SP J Biol Chem. 2005 Sep 2;280(35):31283-93. Epub 2005 Jun 20. PMID:15967794<ref>PMID:15967794</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 2aa2" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Mineralocorticoid receptor\|Mineralocorticoid receptor]]		*[[Mineralocorticoid receptor\|Mineralocorticoid receptor]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Apolito CJ]]		[[Category: Apolito, C J]]
	[[Category: Bledsoe RK]]		[[Category: Bledsoe, R K]]
	[[Category: Holt JA]]		[[Category: Holt, J A]]
	[[Category: Lambert MH]]		[[Category: Lambert, M H]]
	[[Category: Madauss KP]]		[[Category: Madauss, K P]]
	[[Category: Pearce KH]]		[[Category: Pearce, K H]]
	[[Category: Stanley TB]]		[[Category: Stanley, T B]]
	[[Category: Stewart EL]]		[[Category: Stewart, E L]]
	[[Category: Trump RP]]		[[Category: Trump, R P]]
	[[Category: Williams SP]]		[[Category: Williams, S P]]
	[[Category: Willson TM]]		[[Category: Willson, T M]]
			[[Category: Aldosterone]]
			[[Category: Mineralocorticoid]]
			[[Category: Mr]]
			[[Category: Nuclear receptor]]
			[[Category: Steroid receptor]]
			[[Category: Transcription]]

OCA at 11:30, 3 February 2021

2021-02-03T11:30:44Z

← Older revision		Revision as of 11:30, 3 February 2021
Line 1:		Line 1:

	==Mineralocorticoid Receptor with Bound Aldosterone==		==Mineralocorticoid Receptor with Bound Aldosterone==
	<StructureSection load='2aa2' size='340' side='right' caption='[[2aa2]]~~, [[Resolution\|resolution]] 1.95Å~~' scene=''>		<StructureSection load='2aa2' size='340' side='right'caption='[[2aa2]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[2aa2]] 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=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</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=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [https://pdbe.org/2aa2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [https://www.ebi.ac.uk/pdbsum/2aa2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aa2 ProSAT]</span></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2aa5\|2aa5]], [[2aa6\|2aa6]], [[2aa7\|2aa7]]</td></tr>~~
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR3C2, MCR, MLR ([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=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [~~http~~://pdbe.org/2aa2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2aa2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2aa2 ProSAT]</span></td></tr>
	</table>		</table>
	~~== Disease ==~~
	[[http://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[http://omim.org/entry/177735 177735]]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.<ref>PMID:9662404</ref> <ref>PMID:11134129</ref> <ref>PMID:12788847</ref> <ref>PMID:16954160</ref> <ref>PMID:16972228</ref> Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:[http://omim.org/entry/605115 605115]]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.<ref>PMID:9662404</ref> <ref>PMID:15967794</ref> <ref>PMID:15908963</ref> <ref>PMID:10884226</ref>
	~~== Function ==~~
	[[http://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.<ref>PMID:3037703</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/aa/2aa2_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/aa/2aa2_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>
Line 23:		Line 16:
	</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=2aa2 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=2aa2 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand. In addition, most activating ligands hydrogen bond to Thr945 on helix 10. Structural characterization of the naturally occurring S810L mutant explains how stabilization of a helix 3/helix 5 interaction can circumvent the requirement for this hydrogen bond network. Taken together, these results explain the potency of MR activation by aldosterone, the weak activation induced by progesterone and the antihypertensive agent spironolactone, and the binding selectivity of cortisol over cortisone.

	A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor.,Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SP J Biol Chem. 2005 Sep 2;280(35):31283-93. Epub 2005 Jun 20. PMID:15967794<ref>PMID:15967794</ref>		==See Also==
			*[[Mineralocorticoid receptor\|Mineralocorticoid receptor]]
	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 2aa2" style~~=~~"background-color:#fffaf0;"></div>~~
	=~~= References~~ ==
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Large Structures]]
	[[Category: Apolito~~, C J~~]]		[[Category: Apolito CJ]]
	[[Category: Bledsoe~~, R K~~]]		[[Category: Bledsoe RK]]
	[[Category: Holt~~, J A~~]]		[[Category: Holt JA]]
	[[Category: Lambert~~, M H~~]]		[[Category: Lambert MH]]
	[[Category: Madauss~~, K P~~]]		[[Category: Madauss KP]]
	[[Category: Pearce~~, K H~~]]		[[Category: Pearce KH]]
	[[Category: Stanley~~, T B~~]]		[[Category: Stanley TB]]
	[[Category: Stewart~~, E L~~]]		[[Category: Stewart EL]]
	[[Category: Trump~~, R P~~]]		[[Category: Trump RP]]
	[[Category: Williams~~, S P~~]]		[[Category: Williams SP]]
	[[Category: Willson~~, T M]]~~		[[Category: Willson TM]]
	~~[[Category: Aldosterone]]~~
	~~[[Category: Mineralocorticoid]]~~
	~~[[Category: Mr]]~~
	~~[[Category: Nuclear receptor]]~~
	~~[[Category: Steroid receptor]]~~
	~~[[Category: Transcription~~]]

OCA at 08:47, 12 October 2017

2017-10-12T08:47:44Z

← Older revision		Revision as of 08:47, 12 October 2017
Line 1:		Line 1:

	==Mineralocorticoid Receptor with Bound Aldosterone==		==Mineralocorticoid Receptor with Bound Aldosterone==
	<StructureSection load='2aa2' size='340' side='right' caption='[[2aa2]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='2aa2' size='340' side='right' caption='[[2aa2]], [[Resolution\|resolution]] 1.95Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2aa5\|2aa5]], [[2aa6\|2aa6]], [[2aa7\|2aa7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2aa5\|2aa5]], [[2aa6\|2aa6]], [[2aa7\|2aa7]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR3C2, MCR, MLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR3C2, MCR, MLR ([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=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [http://pdbe.org/2aa2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [http://www.ebi.ac.uk/pdbsum/2aa2 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=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [http://pdbe.org/2aa2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [http://www.ebi.ac.uk/pdbsum/2aa2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2aa2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	<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=2aa2 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 07:45, 11 September 2015

2015-09-11T07:45:36Z

← Older revision		Revision as of 07:45, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2aa2' size='340' side='right' caption='[[2aa2]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='2aa2' size='340' side='right' caption='[[2aa2]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2aa2]] 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=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2aa2]] 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=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2aa5\|2aa5]], [[2aa6\|2aa6]], [[2aa7\|2aa7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2aa5\|2aa5]], [[2aa6\|2aa6]], [[2aa7\|2aa7]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR3C2, MCR, MLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR3C2, MCR, MLR ([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=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [http://www.ebi.ac.uk/pdbsum/2aa2 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=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [http://pdbe.org/2aa2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [http://www.ebi.ac.uk/pdbsum/2aa2 PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 30:		Line 30:
	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 2aa2" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Apolito, C J]]		[[Category: Apolito, C J]]
	[[Category: Bledsoe, R K]]		[[Category: Bledsoe, R K]]

OCA at 09:19, 8 January 2015

2015-01-08T09:19:11Z

← Older revision		Revision as of 09:19, 8 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2aa2]] 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=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2aa2]] 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=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2aa5\|2aa5]], [[2aa6\|2aa6]], [[2aa7\|2aa7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2aa5\|2aa5]], [[2aa6\|2aa6]], [[2aa7\|2aa7]]</td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR3C2, MCR, MLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR3C2, MCR, MLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [http://www.ebi.ac.uk/pdbsum/2aa2 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=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [http://www.ebi.ac.uk/pdbsum/2aa2 PDBsum]</span></td></tr>
	<table>		</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[http://omim.org/entry/177735 177735]]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.<ref>PMID:9662404</ref> <ref>PMID:11134129</ref> <ref>PMID:12788847</ref> <ref>PMID:16954160</ref> <ref>PMID:16972228</ref> Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:[http://omim.org/entry/605115 605115]]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.<ref>PMID:9662404</ref> <ref>PMID:15967794</ref> <ref>PMID:15908963</ref> <ref>PMID:10884226</ref>		[[http://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[http://omim.org/entry/177735 177735]]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.<ref>PMID:9662404</ref> <ref>PMID:11134129</ref> <ref>PMID:12788847</ref> <ref>PMID:16954160</ref> <ref>PMID:16972228</ref> Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:[http://omim.org/entry/605115 605115]]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.<ref>PMID:9662404</ref> <ref>PMID:15967794</ref> <ref>PMID:15908963</ref> <ref>PMID:10884226</ref>
Line 35:		Line 35:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Apolito, C J.]]		[[Category: Apolito, C J]]
	[[Category: Bledsoe, R K.]]		[[Category: Bledsoe, R K]]
	[[Category: Holt, J A.]]		[[Category: Holt, J A]]
	[[Category: Lambert, M H.]]		[[Category: Lambert, M H]]
	[[Category: Madauss, K P.]]		[[Category: Madauss, K P]]
	[[Category: Pearce, K H.]]		[[Category: Pearce, K H]]
	[[Category: Stanley, T B.]]		[[Category: Stanley, T B]]
	[[Category: Stewart, E L.]]		[[Category: Stewart, E L]]
	[[Category: Trump, R P.]]		[[Category: Trump, R P]]
	[[Category: Williams, S P.]]		[[Category: Williams, S P]]
	[[Category: Willson, T M.]]		[[Category: Willson, T M]]
	[[Category: Aldosterone]]		[[Category: Aldosterone]]
	[[Category: Mineralocorticoid]]		[[Category: Mineralocorticoid]]

OCA at 00:09, 30 September 2014

2014-09-30T00:09:07Z

← Older revision		Revision as of 00:09, 30 September 2014
Line 1:		Line 1:
	~~{{STRUCTURE_2aa2~~\| ~~PDB~~=2aa2 \| ~~SCENE~~= }}		==Mineralocorticoid Receptor with Bound Aldosterone==
	===~~Mineralocorticoid Receptor with Bound Aldosterone~~===		<StructureSection load='2aa2' size='340' side='right' caption='[[2aa2]], [[Resolution\|resolution]] 1.95Å' scene=''>
	~~{{ABSTRACT_PUBMED_15967794}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[2aa2]] 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=2AA2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AA2 FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AS4:ALDOSTERONE'>AS4</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2aa5\|2aa5]], [[2aa6\|2aa6]], [[2aa7\|2aa7]]</td></tr>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR3C2, MCR, MLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2aa2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aa2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB], [http://www.ebi.ac.uk/pdbsum/2aa2 PDBsum]</span></td></tr>
			<table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[http://omim.org/entry/177735 177735]]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.<ref>PMID:9662404</ref> <ref>PMID:11134129</ref> <ref>PMID:12788847</ref> <ref>PMID:16954160</ref> <ref>PMID:16972228</ref> Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:[http://omim.org/entry/605115 605115]]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.<ref>PMID:9662404</ref> <ref>PMID:15967794</ref> <ref>PMID:15908963</ref> <ref>PMID:10884226</ref>
			== Function ==
			[[http://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.<ref>PMID:3037703</ref>
			== 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/aa/2aa2_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 ==
			Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand. In addition, most activating ligands hydrogen bond to Thr945 on helix 10. Structural characterization of the naturally occurring S810L mutant explains how stabilization of a helix 3/helix 5 interaction can circumvent the requirement for this hydrogen bond network. Taken together, these results explain the potency of MR activation by aldosterone, the weak activation induced by progesterone and the antihypertensive agent spironolactone, and the binding selectivity of cortisol over cortisone.

	~~==Disease==~~		A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor.,Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SP J Biol Chem. 2005 Sep 2;280(35):31283-93. Epub 2005 Jun 20. PMID:15967794<ref>PMID:15967794</ref>
	~~[[http://www~~.~~uniprot~~.~~org/uniprot/MCR_HUMAN MCR_HUMAN]] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant~~ (~~PHA1A~~) [MIM:[http://omim.org/entry/177735 177735]]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.<ref>PMID:9662404</ref><ref>PMID:~~11134129</ref><ref>PMID:12788847</ref><ref>PMID:16954160</ref><ref>PMID:16972228</ref> Defects in NR3C2 are a cause of early~~-~~onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:[http://omim~~.~~org/entry/605115 605115]]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of~~ 20~~, and by suppression of aldosterone secretion~~.~~<ref>~~PMID:~~9662404</ref>~~<ref>PMID:15967794~~</ref><ref>PMID:15908963</ref><ref>PMID:10884226~~</ref>

	~~==Function==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[http:~~/~~/www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol~~. ~~Binds to mineralocorticoid response elements (MRE) and transactivates target genes~~. ~~The effect~~ of ~~MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels~~.<~~ref~~>~~PMID:3037703~~</~~ref~~>		</div>
			== References ==
	~~==About this Structure==~~		<references/>
	[[2aa2]] 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=2AA2 OCA].		__TOC__
			</StructureSection>
	==~~Reference~~==
	~~<ref group="xtra">PMID:015967794</ref>~~<references ~~group="xtra"~~/><~~references~~/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Apolito, C J.]]		[[Category: Apolito, C J.]]

OCA at 03:36, 25 March 2013

2013-03-25T03:36:43Z

← Older revision		Revision as of 03:36, 25 March 2013
Line 1:		Line 1:
	~~[[Image:2aa2.png\|left\|200px]]~~

	{{STRUCTURE_2aa2\| PDB=2aa2 \| SCENE= }}		{{STRUCTURE_2aa2\| PDB=2aa2 \| SCENE= }}
			===Mineralocorticoid Receptor with Bound Aldosterone===
			{{ABSTRACT_PUBMED_15967794}}

	===~~Mineralocorticoid Receptor~~ with ~~Bound Aldosterone===~~		==Disease==
			[[http://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM:[http://omim.org/entry/177735 177735]]. A salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1A is a mild form characterized by target organ defects confined to kidney. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment.<ref>PMID:9662404</ref><ref>PMID:11134129</ref><ref>PMID:12788847</ref><ref>PMID:16954160</ref><ref>PMID:16972228</ref> Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM:[http://omim.org/entry/605115 605115]]. Inheritance is autosomal dominant. The disease is characterized by the onset of severe hypertension before the age of 20, and by suppression of aldosterone secretion.<ref>PMID:9662404</ref><ref>PMID:15967794</ref><ref>PMID:15908963</ref><ref>PMID:10884226</ref>

	~~{{ABSTRACT_PUBMED_15967794}}~~		==Function==
			[[http://www.uniprot.org/uniprot/MCR_HUMAN MCR_HUMAN]] Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.<ref>PMID:3037703</ref>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
	<ref group="xtra">PMID:015967794</ref><references group="xtra"/>		<ref group="xtra">PMID:015967794</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Apolito, C J.]]		[[Category: Apolito, C J.]]

OCA: Protected "2aa2" [edit=sysop:move=sysop]

2013-01-06T09:35:18Z

Protected "2aa2" [edit=sysop:move=sysop]

← Older revision	Revision as of 09:35, 6 January 2013
(No difference)