2aa2: Difference between revisions

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-[[Image:2aa2.gif|left|200px]]
- {{Structure
+==Mineralocorticoid Receptor with Bound Aldosterone==
-|PDB= 2aa2 |SIZE=350|CAPTION= <scene name='initialview01'>2aa2</scene>, resolution 1.950&Aring;
+<StructureSection load='2aa2' size='340' side='right'caption='[[2aa2]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <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>
+<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>
-|ACTIVITY=
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
-|GENE= NR3C2, MCR, MLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<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>
-|DOMAIN=
+<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>
-|RELATEDENTRY=[[2aa5|2AA5]], [[2aa6|2AA6]], [[2aa7|2AA7]]
+</table>
-|RESOURCES=<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.ebi.ac.uk/pdbsum/2aa2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2aa2 RCSB]</span>
+== 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 ==
+[[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/main_output.php?pdb_ID=2aa2 ConSurf].
+<div style="clear:both"></div>
-'''Mineralocorticoid Receptor with Bound Aldosterone'''
+==See Also==
+*[[Mineralocorticoid receptor|Mineralocorticoid receptor]]
+== References ==
-==Overview==
+<references/>
-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.
+__TOC__
+</StructureSection>
-==About this Structure==
-AA2 is a [[Single protein]] structure of 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].
-==Reference==
-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:[http://www.ncbi.nlm.nih.gov/pubmed/15967794 15967794]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[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]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:49:57 2008''