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| - | {{STRUCTURE_1r4i| PDB=1r4i | SCENE= }}
| + | ==Crystal Structure of Androgen Receptor DNA-Binding Domain Bound to a Direct Repeat Response Element== |
| - | ===Crystal Structure of Androgen Receptor DNA-Binding Domain Bound to a Direct Repeat Response Element===
| + | <StructureSection load='1r4i' size='340' side='right' caption='[[1r4i]], [[Resolution|resolution]] 3.10Å' scene=''> |
| - | {{ABSTRACT_PUBMED_15037741}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1r4i]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. The August 2007 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Anabolic Steroids'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2007_8 10.2210/rcsb_pdb/mom_2007_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R4I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1R4I FirstGlance]. <br> |
| | + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br> |
| | + | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</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=1r4i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r4i OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1r4i RCSB], [http://www.ebi.ac.uk/pdbsum/1r4i PDBsum]</span></td></tr> |
| | + | <table> |
| | + | == Disease == |
| | + | [[http://www.uniprot.org/uniprot/ANDR_RAT ANDR_RAT]] Note=Defects in Ar are a cause of androgen insensitivity. Rats with this syndrome are called testicular feminized (TFM).<ref>PMID:2341409</ref> |
| | + | == Function == |
| | + | [[http://www.uniprot.org/uniprot/ANDR_RAT ANDR_RAT]] Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3 (By similarity).<ref>PMID:17181141</ref> <ref>PMID:17008401</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/r4/1r4i_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 == |
| | + | Steroid receptors bind as dimers to a degenerate set of response elements containing inverted repeats of a hexameric half-site separated by 3 bp of spacer (IR3). Naturally occurring selective androgen response elements have recently been identified that resemble direct repeats of the hexameric half-site (ADR3). The 3D crystal structure of the androgen receptor (AR) DNA-binding domain bound to a selective ADR3 reveals an unexpected head-to-head arrangement of the two protomers rather than the expected head-to-tail arrangement seen in nuclear receptors bound to response elements of similar geometry. Compared with the glucocorticoid receptor, the DNA-binding domain dimer interface of the AR has additional interactions that stabilize the AR dimer and increase the affinity for nonconsensus response elements. This increased interfacial stability compared with the other steroid receptors may account for the selective binding of AR to ADR3 response elements. |
| | | | |
| - | ==Disease==
| + | Structural basis of androgen receptor binding to selective androgen response elements.,Shaffer PL, Jivan A, Dollins DE, Claessens F, Gewirth DT Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4758-63. Epub 2004 Mar 22. PMID:15037741<ref>PMID:15037741</ref> |
| - | [[http://www.uniprot.org/uniprot/ANDR_RAT ANDR_RAT]] Note=Defects in Ar are a cause of androgen insensitivity. Rats with this syndrome are called testicular feminized (TFM).<ref>PMID:2341409</ref>
| + | |
| | | | |
| - | ==Function==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[http://www.uniprot.org/uniprot/ANDR_RAT ANDR_RAT]] Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3 (By similarity).<ref>PMID:17181141</ref><ref>PMID:17008401</ref>
| + | </div> |
| | | | |
| - | ==About this Structure== | + | ==See Also== |
| - | [[1r4i]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. The August 2007 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Anabolic Steroids'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2007_8 10.2210/rcsb_pdb/mom_2007_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R4I OCA]. | + | *[[Androgen receptor|Androgen receptor]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:015037741</ref><references group="xtra"/><references/>
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Anabolic Steroids]] | | [[Category: Anabolic Steroids]] |
| | [[Category: RCSB PDB Molecule of the Month]] | | [[Category: RCSB PDB Molecule of the Month]] |
| Structural highlights
1r4i is a 4 chain structure with sequence from Rattus norvegicus. The August 2007 RCSB PDB Molecule of the Month feature on Anabolic Steroids by David S. Goodsell is 10.2210/rcsb_pdb/mom_2007_8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: |
| | Gene: | AR (Rattus norvegicus) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[ANDR_RAT] Note=Defects in Ar are a cause of androgen insensitivity. Rats with this syndrome are called testicular feminized (TFM).[1]
Function
[ANDR_RAT] Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3 (By similarity).[2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Steroid receptors bind as dimers to a degenerate set of response elements containing inverted repeats of a hexameric half-site separated by 3 bp of spacer (IR3). Naturally occurring selective androgen response elements have recently been identified that resemble direct repeats of the hexameric half-site (ADR3). The 3D crystal structure of the androgen receptor (AR) DNA-binding domain bound to a selective ADR3 reveals an unexpected head-to-head arrangement of the two protomers rather than the expected head-to-tail arrangement seen in nuclear receptors bound to response elements of similar geometry. Compared with the glucocorticoid receptor, the DNA-binding domain dimer interface of the AR has additional interactions that stabilize the AR dimer and increase the affinity for nonconsensus response elements. This increased interfacial stability compared with the other steroid receptors may account for the selective binding of AR to ADR3 response elements.
Structural basis of androgen receptor binding to selective androgen response elements.,Shaffer PL, Jivan A, Dollins DE, Claessens F, Gewirth DT Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4758-63. Epub 2004 Mar 22. PMID:15037741[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yarbrough WG, Quarmby VE, Simental JA, Joseph DR, Sar M, Lubahn DB, Olsen KL, French FS, Wilson EM. A single base mutation in the androgen receptor gene causes androgen insensitivity in the testicular feminized rat. J Biol Chem. 1990 May 25;265(15):8893-900. PMID:2341409
- ↑ Sun C, Robl JA, Wang TC, Huang Y, Kuhns JE, Lupisella JA, Beehler BC, Golla R, Sleph PG, Seethala R, Fura A, Krystek SR Jr, An Y, Malley MF, Sack JS, Salvati ME, Grover GJ, Ostrowski J, Hamann LG. Discovery of potent, orally-active, and muscle-selective androgen receptor modulators based on an N-aryl-hydroxybicyclohydantoin scaffold. J Med Chem. 2006 Dec 28;49(26):7596-9. PMID:17181141 doi:10.1021/jm061101w
- ↑ Ostrowski J, Kuhns JE, Lupisella JA, Manfredi MC, Beehler BC, Krystek SR Jr, Bi Y, Sun C, Seethala R, Golla R, Sleph PG, Fura A, An Y, Kish KF, Sack JS, Mookhtiar KA, Grover GJ, Hamann LG. Pharmacological and x-ray structural characterization of a novel selective androgen receptor modulator: potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats. Endocrinology. 2007 Jan;148(1):4-12. Epub 2006 Sep 28. PMID:17008401 doi:10.1210/en.2006-0843
- ↑ Shaffer PL, Jivan A, Dollins DE, Claessens F, Gewirth DT. Structural basis of androgen receptor binding to selective androgen response elements. Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4758-63. Epub 2004 Mar 22. PMID:15037741 doi:10.1073/pnas.0401123101
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