9gc7: Difference between revisions

Latest revision as of 07:02, 18 February 2026

Mineralocorticoid receptor in complex with acylurea antagonists.

Structural highlights

9gc7 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.46Å
Ligands:	A1IJ6, MPD, NHE
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MCR_HUMAN Defects in NR3C2 are a cause of pseudohypoaldosteronism 1, autosomal dominant (PHA1A) [MIM: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.^[1] ^[2] ^[3] ^[4] ^[5] Defects in NR3C2 are a cause of early-onset hypertension with severe exacerbation in pregnancy (EOHSEP) [MIM: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.^[6] ^[7] ^[8] ^[9]

Function

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.^[10]

References

↑ Geller DS, Rodriguez-Soriano J, Vallo Boado A, Schifter S, Bayer M, Chang SS, Lifton RP. Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. Nat Genet. 1998 Jul;19(3):279-81. PMID:9662404 doi:10.1038/966
↑ Tajima T, Kitagawa H, Yokoya S, Tachibana K, Adachi M, Nakae J, Suwa S, Katoh S, Fujieda K. A novel missense mutation of mineralocorticoid receptor gene in one Japanese family with a renal form of pseudohypoaldosteronism type 1. J Clin Endocrinol Metab. 2000 Dec;85(12):4690-4. PMID:11134129
↑ Sartorato P, Lapeyraque AL, Armanini D, Kuhnle U, Khaldi Y, Salomon R, Abadie V, Di Battista E, Naselli A, Racine A, Bosio M, Caprio M, Poulet-Young V, Chabrolle JP, Niaudet P, De Gennes C, Lecornec MH, Poisson E, Fusco AM, Loli P, Lombes M, Zennaro MC. Different inactivating mutations of the mineralocorticoid receptor in fourteen families affected by type I pseudohypoaldosteronism. J Clin Endocrinol Metab. 2003 Jun;88(6):2508-17. PMID:12788847
↑ Riepe FG, Finkeldei J, de Sanctis L, Einaudi S, Testa A, Karges B, Peter M, Viemann M, Grotzinger J, Sippell WG, Fejes-Toth G, Krone N. Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1. J Clin Endocrinol Metab. 2006 Nov;91(11):4552-61. Epub 2006 Sep 5. PMID:16954160 doi:jc.2006-1161
↑ Pujo L, Fagart J, Gary F, Papadimitriou DT, Claes A, Jeunemaitre X, Zennaro MC. Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism. Hum Mutat. 2007 Jan;28(1):33-40. PMID:16972228 doi:10.1002/humu.20371
↑ Geller DS, Rodriguez-Soriano J, Vallo Boado A, Schifter S, Bayer M, Chang SS, Lifton RP. Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. Nat Genet. 1998 Jul;19(3):279-81. PMID:9662404 doi:10.1038/966
↑ Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SP. A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor. J Biol Chem. 2005 Sep 2;280(35):31283-93. Epub 2005 Jun 20. PMID:15967794 doi:https://dx.doi.org/10.1074/jbc.M504098200
↑ Fagart J, Huyet J, Pinon GM, Rochel M, Mayer C, Rafestin-Oblin ME. Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension. Nat Struct Mol Biol. 2005 Jun;12(6):554-5. Epub 2005 May 22. PMID:15908963 doi:10.1038/nsmb939
↑ Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A, Meinke G, Tsai FT, Sigler PB, Lifton RP. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 2000 Jul 7;289(5476):119-23. PMID:10884226
↑ Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, Evans RM. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science. 1987 Jul 17;237(4812):268-75. PMID:3037703

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OCA

[1] Geller DS, Rodriguez-Soriano J, Vallo Boado A, Schifter S, Bayer M, Chang SS, Lifton RP. Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. Nat Genet. 1998 Jul;19(3):279-81. PMID:9662404 doi:10.1038/966

[2] Tajima T, Kitagawa H, Yokoya S, Tachibana K, Adachi M, Nakae J, Suwa S, Katoh S, Fujieda K. A novel missense mutation of mineralocorticoid receptor gene in one Japanese family with a renal form of pseudohypoaldosteronism type 1. J Clin Endocrinol Metab. 2000 Dec;85(12):4690-4. PMID:11134129

[3] Sartorato P, Lapeyraque AL, Armanini D, Kuhnle U, Khaldi Y, Salomon R, Abadie V, Di Battista E, Naselli A, Racine A, Bosio M, Caprio M, Poulet-Young V, Chabrolle JP, Niaudet P, De Gennes C, Lecornec MH, Poisson E, Fusco AM, Loli P, Lombes M, Zennaro MC. Different inactivating mutations of the mineralocorticoid receptor in fourteen families affected by type I pseudohypoaldosteronism. J Clin Endocrinol Metab. 2003 Jun;88(6):2508-17. PMID:12788847

[4] Riepe FG, Finkeldei J, de Sanctis L, Einaudi S, Testa A, Karges B, Peter M, Viemann M, Grotzinger J, Sippell WG, Fejes-Toth G, Krone N. Elucidating the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1. J Clin Endocrinol Metab. 2006 Nov;91(11):4552-61. Epub 2006 Sep 5. PMID:16954160 doi:jc.2006-1161

[5] Pujo L, Fagart J, Gary F, Papadimitriou DT, Claes A, Jeunemaitre X, Zennaro MC. Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism. Hum Mutat. 2007 Jan;28(1):33-40. PMID:16972228 doi:10.1002/humu.20371

[6] Geller DS, Rodriguez-Soriano J, Vallo Boado A, Schifter S, Bayer M, Chang SS, Lifton RP. Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. Nat Genet. 1998 Jul;19(3):279-81. PMID:9662404 doi:10.1038/966

[7] Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SP. A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor. J Biol Chem. 2005 Sep 2;280(35):31283-93. Epub 2005 Jun 20. PMID:15967794 doi:https://dx.doi.org/10.1074/jbc.M504098200

[8] Fagart J, Huyet J, Pinon GM, Rochel M, Mayer C, Rafestin-Oblin ME. Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension. Nat Struct Mol Biol. 2005 Jun;12(6):554-5. Epub 2005 May 22. PMID:15908963 doi:10.1038/nsmb939

[9] Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A, Meinke G, Tsai FT, Sigler PB, Lifton RP. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 2000 Jul 7;289(5476):119-23. PMID:10884226

[10] Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman DE, Evans RM. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science. 1987 Jul 17;237(4812):268-75. PMID:3037703

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[2]

[3]

[4]

[5]

[6]

[7]

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[10]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9gc7 is ON HOLD  until Paper Publication
+==Mineralocorticoid receptor in complex with acylurea antagonists.==
+<StructureSection load='9gc7' size='340' side='right'caption='[[9gc7]], [[Resolution|resolution]] 1.46&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9gc7]] is a 2 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=9GC7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9GC7 FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.46&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1IJ6:(2~{S})-~{N}-aminocarbonyl-2-[(4-cyano-6-cyclopropyl-cyclohexa-1,2,3,5-tetraen-1-yl)amino]propanamide'>A1IJ6</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</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=9gc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9gc7 OCA], [https://pdbe.org/9gc7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9gc7 RCSB], [https://www.ebi.ac.uk/pdbsum/9gc7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9gc7 ProSAT]</span></td></tr>
+</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>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Aagaard A]]
+[[Category: Barlind L]]
+[[Category: Edman K]]

9gc7: Difference between revisions

Latest revision as of 07:02, 18 February 2026

Mineralocorticoid receptor in complex with acylurea antagonists.

Structural highlights

Disease

Function

References

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