PDBsum entry 1lat

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protein dna_rna metals links
Transcription/DNA PDB id
Protein chains
71 a.a. *
_ZN ×4
Waters ×316
* Residue conservation analysis
PDB id:
Name: Transcription/DNA
Title: Glucocorticoid receptor mutant/DNA complex
Structure: DNA (5'- d( Tp Tp Cp Cp Ap Gp Ap Ap Cp Ap Tp Gp Tp Tp Cp Tp G p Gp A chain: c, d. Engineered: yes. Glucocorticoid receptor. Chain: a, b. Engineered: yes. Mutation: yes
Source: Synthetic: yes. Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: nr3c1, grl. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
1.90Å     R-factor:   0.195     R-free:   0.281
Authors: D.T.Gewirth,P.B.Sigler
Key ref: D.T.Gewirth and P.B.Sigler (1995). The basis for half-site specificity explored through a non-cognate steroid receptor-DNA complex. Nat Struct Biol, 2, 386-394. PubMed id: 7664096
18-Dec-95     Release date:   03-Apr-96    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P06536  (GCR_RAT) -  Glucocorticoid receptor
795 a.a.
71 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 10 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     DNA binding     5 terms  


Nat Struct Biol 2:386-394 (1995)
PubMed id: 7664096  
The basis for half-site specificity explored through a non-cognate steroid receptor-DNA complex.
D.T.Gewirth, P.B.Sigler.
Steroid receptors recognize bipartite targets composed of six base-pair half-sites. There are two canonical types of half-site which differ only in their central two base pairs. The crystal structure of an estrogen receptor-like DNA-binding domain bound to the wrong type of half-site (a glucocorticoid response element) reveals an interface that resembles the specific interfaces of the glucocorticoid receptor or estrogen receptor bound to their correct response elements. The underlying stereochemical defect that weakens the non-cognate interface is a difference in the helical geometry of the incorrect DNA half-site which prevents a side-chain contact and results in a gap which is filled by at least five additional fixed water sites, imposing a potential entropic burden on the stability of the interface.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20422012 Y.Ciribilli, V.Andreotti, D.Menendez, J.S.Langen, G.Schoenfelder, M.A.Resnick, and A.Inga (2010).
The coordinated p53 and estrogen receptor cis-regulation at an FLT1 promoter SNP is specific to genotoxic stress and estrogenic compound.
  PLoS One, 5, e10236.  
19522502 G.M.Clore, and J.Iwahara (2009).
Theory, practice, and applications of paramagnetic relaxation enhancement for the characterization of transient low-population states of biological macromolecules and their complexes.
  Chem Rev, 109, 4108-4139.  
17163421 R.Chmelar, G.Buchanan, E.F.Need, W.Tilley, and N.M.Greenberg (2007).
Androgen receptor coregulators and their involvement in the development and progression of prostate cancer.
  Int J Cancer, 120, 719-733.  
17464340 V.Vijayanathan, N.J.Greenfield, T.J.Thomas, M.M.Ivanova, V.V.Tyulmenkov, C.M.Klinge, M.A.Gallo, and T.Thomas (2007).
Effects of estradiol and 4-hydroxytamoxifen on the conformation, thermal stability, and DNA recognition of estrogen receptor beta.
  Biochem Cell Biol, 85, 1.  
16497933 A.Banerjee, W.L.Santos, and G.L.Verdine (2006).
Structure of a DNA glycosylase searching for lesions.
  Science, 311, 1153-1157.
PDB codes: 2f5n 2f5o 2f5p 2f5q 2f5s
17008406 J.Iwahara, M.Zweckstetter, and G.M.Clore (2006).
NMR structural and kinetic characterization of a homeodomain diffusing and hopping on nonspecific DNA.
  Proc Natl Acad Sci U S A, 103, 15062-15067.  
15869395 A.Sarai, and H.Kono (2005).
Protein-DNA recognition patterns and predictions.
  Annu Rev Biophys Biomol Struct, 34, 379-398.  
15846405 Y.Tanaka, and K.Taira (2005).
Detection of RNA nucleobase metalation by NMR spectroscopy.
  Chem Commun (Camb), (), 2069-2079.  
15037741 P.L.Shaffer, A.Jivan, D.E.Dollins, F.Claessens, and D.T.Gewirth (2004).
Structural basis of androgen receptor binding to selective androgen response elements.
  Proc Natl Acad Sci U S A, 101, 4758-4763.
PDB code: 1r4i
12784213 J.Aishima, and C.Wolberger (2003).
Insights into nonspecific binding of homeodomains from a structure of MATalpha2 bound to DNA.
  Proteins, 51, 544-551.  
12065400 C.G.Kalodimos, A.M.Bonvin, R.K.Salinas, R.Wechselberger, R.Boelens, and R.Kaptein (2002).
Plasticity in protein-DNA recognition: lac repressor interacts with its natural operator 01 through alternative conformations of its DNA-binding domain.
  EMBO J, 21, 2866-2876.
PDB code: 1l1m
11980721 P.L.Shaffer, and D.T.Gewirth (2002).
Structural basis of VDR-DNA interactions on direct repeat response elements.
  EMBO J, 21, 2242-2252.
PDB codes: 1kb2 1kb4 1kb6
11179889 F.Rastinejad (2001).
Retinoid X receptor and its partners in the nuclear receptor family.
  Curr Opin Struct Biol, 11, 33-38.  
  11243468 H.Hauksdóttir, and M.L.Privalsky (2001).
DNA recognition by the aberrant retinoic acid receptors implicated in human acute promyelocytic leukemia.
  Cell Growth Differ, 12, 85-98.  
11406412 S.Khorasanizadeh, and F.Rastinejad (2001).
Nuclear-receptor interactions on DNA-response elements.
  Trends Biochem Sci, 26, 384-390.  
10698945 F.Rastinejad, T.Wagner, Q.Zhao, and S.Khorasanizadeh (2000).
Structure of the RXR-RAR DNA-binding complex on the retinoic acid response element DR1.
  EMBO J, 19, 1045-1054.
PDB code: 1dsz
  11206057 J.W.Cave, W.Kremer, and D.E.Wemmer (2000).
Backbone dynamics of sequence specific recognition and binding by the yeast Pho4 bHLH domain probed by NMR.
  Protein Sci, 9, 2354-2365.  
10698952 J.Y.Lee, C.Chang, H.K.Song, J.Moon, J.K.Yang, H.K.Kim, S.T.Kwon, and S.W.Suh (2000).
Crystal structure of NAD(+)-dependent DNA ligase: modular architecture and functional implications.
  EMBO J, 19, 1119-1129.
PDB codes: 1dgs 1dgt 1v9p
11250728 M.Ruff, M.Gangloff, J.M.Wurtz, and D.Moras (2000).
Estrogen receptor transcription and transactivation: Structure-function relationship in DNA- and ligand-binding domains of estrogen receptors.
  Breast Cancer Res, 2, 353-359.  
10500115 E.L.Cunningham, S.S.Jaswal, J.L.Sohl, and D.A.Agard (1999).
Kinetic stability as a mechanism for protease longevity.
  Proc Natl Acad Sci U S A, 96, 11008-11014.  
10090291 H.Kono, and A.Sarai (1999).
Structure-based prediction of DNA target sites by regulatory proteins.
  Proteins, 35, 114-131.  
9927650 J.F.Schildbach, A.W.Karzai, B.E.Raumann, and R.T.Sauer (1999).
Origins of DNA-binding specificity: role of protein contacts with the DNA backbone.
  Proc Natl Acad Sci U S A, 96, 811-817.
PDB codes: 1baz 1bdt 1bdv
10026283 K.Nadassy, S.J.Wodak, and J.Janin (1999).
Structural features of protein-nucleic acid recognition sites.
  Biochemistry, 38, 1999-2017.  
10665831 M.K.Agarwal, and M.Mirshahi (1999).
General overview of mineralocorticoid hormone action.
  Pharmacol Ther, 84, 273-326.  
9482860 C.R.Robinson, and S.G.Sligar (1998).
Changes in solvation during DNA binding and cleavage are critical to altered specificity of the EcoRI endonuclease.
  Proc Natl Acad Sci U S A, 95, 2186-2191.  
9705308 N.C.Horton, and J.J.Perona (1998).
Recognition of flanking DNA sequences by EcoRV endonuclease involves alternative patterns of water-mediated contacts.
  J Biol Chem, 273, 21721-21729.
PDB code: 1bgb
  9684880 R.A.Albright, M.C.Mossing, and B.W.Matthews (1998).
Crystal structure of an engineered Cro monomer bound nonspecifically to DNA: possible implications for nonspecific binding by the wild-type protein.
  Protein Sci, 7, 1485-1494.
PDB code: 3orc
9251777 D.Kosztin, T.C.Bishop, and K.Schulten (1997).
Binding of the estrogen receptor to DNA. The role of waters.
  Biophys J, 73, 557-570.  
9287161 H.Berglund, M.Wolf-Watz, T.Lundbäck, S.van den Berg, and T.Härd (1997).
Structure and dynamics of the glucocorticoid receptor DNA-binding domain: comparison of wild type and a mutant with altered specificity.
  Biochemistry, 36, 11188-11197.  
9032063 J.W.Schwabe (1997).
The role of water in protein-DNA interactions.
  Curr Opin Struct Biol, 7, 126-134.  
9782776 R.E.Dickerson, and T.K.Chiu (1997).
Helix bending as a factor in protein/DNA recognition.
  Biopolymers, 44, 361-403.  
9129808 T.C.Bishop, D.Kosztin, and K.Schulten (1997).
How hormone receptor-DNA binding affects nucleosomal DNA: the role of symmetry.
  Biophys J, 72, 2056-2067.  
8702636 C.C.Nelson, S.C.Hendy, J.S.Faris, and P.J.Romaniuk (1996).
Retinoid X receptor alters the determination of DNA binding specificity by the P-box amino acids of the thyroid hormone receptor.
  J Biol Chem, 271, 19464-19474.  
8994885 M.A.Navia (1996).
Protein-drug complexes important for immunoregulation and organ transplantation.
  Curr Opin Struct Biol, 6, 838-847.  
8901570 N.Y.Sidorova, and D.C.Rau (1996).
Differences in water release for the binding of EcoRI to specific and nonspecific DNA sequences.
  Proc Natl Acad Sci U S A, 93, 12272-12277.  
8643475 T.Lundbäck, and T.Härd (1996).
Sequence-specific DNA-binding dominated by dehydration.
  Proc Natl Acad Sci U S A, 93, 4754-4759.  
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 codes are shown on the right.