PDBsum entry 2a3i

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Transferase PDB id
Protein chains
253 a.a. *
12 a.a. *
Waters ×160
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor
Structure: Mineralocorticoid receptor. Chain: a. Fragment: mineralocoricoid receptor. Synonym: mr. Engineered: yes. Mutation: yes. Nuclear receptor coactivator 1, residues 1430- 1441. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: nr3c2, mcr, mlr. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this sequence occurs naturally in homo sapiens (humans).
Biol. unit: Dimer (from PQS)
1.95Å     R-factor:   0.222     R-free:   0.253
Authors: Y.Li,K.Suino,J.Daugherty,H.E.Xu
Key ref:
Y.Li et al. (2005). Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor. Mol Cell, 19, 367-380. PubMed id: 16061183 DOI: 10.1016/j.molcel.2005.06.026
24-Jun-05     Release date:   19-Jul-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08235  (MCR_HUMAN) -  Mineralocorticoid receptor
984 a.a.
253 a.a.*
Protein chain
Pfam   ArchSchema ?
Q15788  (NCOA1_HUMAN) -  Nuclear receptor coactivator 1
1441 a.a.
12 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain B: E.C.  - Histone acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + [histone] = CoA + acetyl-[histone]
+ [histone]
= CoA
+ acetyl-[histone]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   2 terms 
  Biochemical function     DNA binding     3 terms  


    Added reference    
DOI no: 10.1016/j.molcel.2005.06.026 Mol Cell 19:367-380 (2005)
PubMed id: 16061183  
Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor.
Y.Li, K.Suino, J.Daugherty, H.E.Xu.
Mineralocorticoid receptor (MR) controls sodium homeostasis and blood pressure through hormone binding and coactivator recruitment. Here, we report a 1.95 A crystal structure of the MR ligand binding domain containing a single C808S mutation bound to corticosterone and the fourth LXXLL motif of steroid receptor coactivator-1 (SRC1-4). Through a combination of biochemical and structural analyses, we demonstrate that SRC1-4 is the most potent MR binding motif and mutations that disrupt the MR/SRC1-4 interactions abolish the ability of the full-length SRC1 to coactivate MR. The structure also reveals a compact steroid binding pocket with a unique topology that is primarily defined by key residues of helices 6 and 7. Mutations swapping a single residue at position 848 from helix H7 between MR and glucocorticoid receptor (GR) switch their hormone specificity. Together, these findings provide critical insights into the molecular basis of hormone binding and coactivator recognition by MR and related steroid receptors.
  Selected figure(s)  
Figure 3.
Figure 3. Recognition of the SRC1-4 LXXLL Motif and Coactivator Assembly by MR
Figure 5.
Figure 5. Recognition of Corticosterone by MR and Ligand Binding Specificity of GR and MR
  The above figures are reprinted by permission from Cell Press: Mol Cell (2005, 19, 367-380) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20054001 A.Murai-Takeda, H.Shibata, I.Kurihara, S.Kobayashi, K.Yokota, N.Suda, Y.Mitsuishi, R.Jo, H.Kitagawa, S.Kato, T.Saruta, and H.Itoh (2010).
NF-YC functions as a corepressor of agonist-bound mineralocorticoid receptor.
  J Biol Chem, 285, 8084-8093.  
20333619 A.S.Veleiro, L.D.Alvarez, S.L.Eduardo, and G.Burton (2010).
Structure of the glucocorticoid receptor, a flexible protein that can adapt to different ligands.
  ChemMedChem, 5, 649-659.  
20723571 L.Jin, and Y.Li (2010).
Structural and functional insights into nuclear receptor signaling.
  Adv Drug Deliv Rev, 62, 1218-1226.  
20413295 M.J.Harms, and J.W.Thornton (2010).
Analyzing protein structure and function using ancestral gene reconstruction.
  Curr Opin Struct Biol, 20, 360-366.  
20148675 P.Huang, V.Chandra, and F.Rastinejad (2010).
Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics.
  Annu Rev Physiol, 72, 247-272.  
19995608 X.E.Zhou, K.Suino-Powell, P.L.Ludidi, D.P.McDonnell, and H.E.Xu (2010).
Expression, purification and primary crystallographic study of human androgen receptor in complex with DNA and coactivator motifs.
  Protein Expr Purif, 71, 21-27.  
19114086 C.D.Clyne, C.Y.Chang, R.Safi, P.J.Fuller, D.P.McDonnell, and M.J.Young (2009).
Purification and characterization of recombinant human mineralocorticoid receptor.
  Mol Cell Endocrinol, 302, 81-85.  
19442333 F.McManus, S.M.Mackenzie, and E.M.Freel (2009).
Central mineralocorticoid receptors, sympathetic activity, and hypertension.
  Curr Hypertens Rep, 11, 224-230.  
19638349 L.R.Stow, M.L.Gumz, I.J.Lynch, M.M.Greenlee, A.Rudin, B.D.Cain, and C.S.Wingo (2009).
Aldosterone modulates steroid receptor binding to the endothelin-1 gene (edn1).
  J Biol Chem, 284, 30087-30096.  
19557178 M.E.Baker, D.J.Chang, and C.Chandsawangbhuwana (2009).
3D model of lamprey estrogen receptor with estradiol and 15alpha-hydroxy-estradiol.
  PLoS One, 4, e6038.  
19006237 P.Escher, P.Gouras, R.Roduit, L.Tiab, S.Bolay, T.Delarive, S.Chen, C.C.Tsai, M.Hayashi, J.Zernant, J.E.Merriam, N.Mermod, R.Allikmets, F.L.Munier, and D.F.Schorderet (2009).
Mutations in NR2E3 can cause dominant or recessive retinal degenerations in the same family.
  Hum Mutat, 30, 342-351.  
18502379 J.Zhang, and D.S.Geller (2008).
Helix 3-helix 5 interactions in steroid hormone receptor function.
  J Steroid Biochem Mol Biol, 109, 279-285.  
18160712 K.Suino-Powell, Y.Xu, C.Zhang, Y.G.Tao, W.D.Tolbert, S.S.Simons, and H.E.Xu (2008).
Doubling the size of the glucocorticoid receptor ligand binding pocket by deacylcortivazol.
  Mol Cell Biol, 28, 1915-1923.
PDB code: 3bqd
18277151 M.J.Young (2008).
Mechanisms of mineralocorticoid receptor-mediated cardiac fibrosis and vascular inflammation.
  Curr Opin Nephrol Hypertens, 17, 174-180.  
18798693 S.W.Kruse, K.Suino-Powell, X.E.Zhou, J.E.Kretschman, R.Reynolds, C.Vonrhein, Y.Xu, L.Wang, S.Y.Tsai, M.J.Tsai, and H.E.Xu (2008).
Identification of COUP-TFII orphan nuclear receptor as a retinoic acid-activated receptor.
  PLoS Biol, 6, e227.
PDB code: 3cjw
18469005 Y.Li, A.Kovach, K.Suino-Powell, D.Martynowski, and H.E.Xu (2008).
Structural and biochemical basis for the binding selectivity of peroxisome proliferator-activated receptor gamma to PGC-1alpha.
  J Biol Chem, 283, 19132-19139.
PDB code: 3cs8
17137423 D.L.Bain, A.F.Heneghan, K.D.Connaghan-Jones, and M.T.Miura (2007).
Nuclear receptor structure: implications for function.
  Annu Rev Physiol, 69, 201-220.  
17105732 K.Yokota, H.Shibata, I.Kurihara, S.Kobayashi, N.Suda, A.Murai-Takeda, I.Saito, H.Kitagawa, S.Kato, T.Saruta, and H.Itoh (2007).
Coactivation of the N-terminal transactivation of mineralocorticoid receptor by Ubc9.
  J Biol Chem, 282, 1998-2010.  
16972228 L.Pujo, J.Fagart, F.Gary, D.T.Papadimitriou, A.Claës, X.Jeunemaître, and M.C.Zennaro (2007).
Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism.
  Hum Mutat, 28, 33-40.  
17306029 M.E.Baker, C.Chandsawangbhuwana, and N.Ollikainen (2007).
Structural analysis of the evolution of steroid specificity in the mineralocorticoid and glucocorticoid receptors.
  BMC Evol Biol, 7, 24.  
18174920 S.Viengchareun, D.Le Menuet, L.Martinerie, M.Munier, L.Pascual-Le Tallec, and M.Lombès (2007).
The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology.
  Nucl Recept Signal, 5, e012.  
16601189 J.T.Bridgham, S.M.Carroll, and J.W.Thornton (2006).
Evolution of hormone-receptor complexity by molecular exploitation.
  Science, 312, 97.  
16503757 P.Fuller (2006).
The aldosterone receptor--new insights?
  Expert Opin Investig Drugs, 15, 201-203.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.