2ihq

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of the Rat Androgen Receptor Ligand Binding Domian Complex with an N-Aryl-Hydroxybicyclohydantoin

Structural highlights

2ihq 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

A novel, N-aryl-bicyclohydantoin selective androgen receptor modulator scaffold was discovered through structure-guided modifications of androgen receptor antagonists. A prototype compound (7R,7aS)-10b from this series is a potent and highly tissue-selective agonist of the androgen receptor. After oral dosing in a rat atrophied levator ani muscle model, (7R,7aS)-10b demonstrated efficacy at restoring levator ani muscle mass to that of intact controls and exhibited >50-fold selectivity for muscle over prostate.

Discovery of potent, orally-active, and muscle-selective androgen receptor modulators based on an N-aryl-hydroxybicyclohydantoin scaffold.,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 J Med Chem. 2006 Dec 28;49(26):7596-9. PMID:17181141^[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
↑ 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

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/2ihq"

Categories: Large Structures | Rattus norvegicus | Sack JS

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the Rat Androgen Receptor Ligand Binding Domian Complex with an N-Aryl-Hydroxybicyclohydantoin==
-<StructureSection load='2ihq' size='340' side='right' caption='[[2ihq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='2ihq' size='340' side='right'caption='[[2ihq]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2ihq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IHQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2IHQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2ihq]] 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=2IHQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IHQ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LG7:4-[(7R,7AS)-7-HYDROXY-1,3-DIOXOTETRAHYDRO-1H-PYRROLO[1,2-C]IMIDAZOL-2(3H)-YL]-1-NAPHTHONITRILE'>LG7</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">[[1i37|1i37]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LG7:4-[(7R,7AS)-7-HYDROXY-1,3-DIOXOTETRAHYDRO-1H-PYRROLO[1,2-C]IMIDAZOL-2(3H)-YL]-1-NAPHTHONITRILE'>LG7</scene></td></tr>
-<tr id='gene'><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 Buffalo rat])</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=2ihq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ihq OCA], [https://pdbe.org/2ihq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ihq RCSB], [https://www.ebi.ac.uk/pdbsum/2ihq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ihq ProSAT]</span></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=2ihq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ihq OCA], [http://pdbe.org/2ihq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ihq RCSB], [http://www.ebi.ac.uk/pdbsum/2ihq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ihq 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 34: / Line 33: @@
 ==See Also==
-*[[Androgen receptor|Androgen receptor]]
+*[[Androgen receptor 3D structures|Androgen receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Buffalo rat]]
+[[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]]

2ihq

From Proteopedia

Current revision

Crystal Structure of the Rat Androgen Receptor Ligand Binding Domian Complex with an N-Aryl-Hydroxybicyclohydantoin

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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