1i37

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF THE RAT ANDROGEN RECEPTOR LIGAND BINDING DOMAIN COMPLEX WITH DIHYDROTESTOSTERONE

Structural highlights

1i37 is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

The structures of the ligand-binding domains (LBD) of the wild-type androgen receptor (AR) and the T877A mutant corresponding to that in LNCaP cells, both bound to dihydrotestosterone, have been refined at 2.0 A resolution. In contrast to the homodimer seen in the retinoid-X receptor and estrogen receptor LBD structures, the AR LBD is monomeric, possibly because of the extended C terminus of AR, which lies in a groove at the dimerization interface. Binding of the natural ligand dihydrotestosterone by the mutant LBD involves interactions with the same residues as in the wild-type receptor, with the exception of the side chain of threonine 877, which is an alanine residue in the mutant. This structural difference in the binding pocket can explain the ability of the mutant AR found in LNCaP cells (T877A) to accommodate progesterone and other ligands that the wild-type receptor cannot.

Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone.,Sack JS, Kish KF, Wang C, Attar RM, Kiefer SE, An Y, Wu GY, Scheffler JE, Salvati ME, Krystek SR Jr, Weinmann R, Einspahr HM Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4904-9. PMID:11320241^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Sack JS, Kish KF, Wang C, Attar RM, Kiefer SE, An Y, Wu GY, Scheffler JE, Salvati ME, Krystek SR Jr, Weinmann R, Einspahr HM. Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):4904-9. PMID:11320241 doi:10.1073/pnas.081565498

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1i37"

Categories: Large Structures | Rattus norvegicus | Sack JS

@@ Line 3: / Line 3: @@
 <StructureSection load='1i37' size='340' side='right'caption='[[1i37]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1i37]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I37 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1I37 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1i37]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I37 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1I37 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1i38|1i38]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1i37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i37 OCA], [http://pdbe.org/1i37 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1i37 RCSB], [http://www.ebi.ac.uk/pdbsum/1i37 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1i37 ProSAT]</span></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=1i37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1i37 OCA], [https://pdbe.org/1i37 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1i37 RCSB], [https://www.ebi.ac.uk/pdbsum/1i37 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1i37 ProSAT]</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>
+[https://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>
+[https://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]]
@@ Line 39: / Line 39: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Sack, J S]]
+[[Category: Rattus norvegicus]]
-[[Category: Androgen receptor]]
+[[Category: Sack JS]]
-[[Category: Hormone-growth factor complex]]
-[[Category: Ligand-binding domain]]
-[[Category: Nuclear receptor]]
-[[Category: Steroid receptor]]
-[[Category: Transcription regulation]]

1i37

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF THE RAT ANDROGEN RECEPTOR LIGAND BINDING DOMAIN COMPLEX WITH DIHYDROTESTOSTERONE

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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