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1xnn

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Revision as of 07:37, 18 April 2018

CRYSTAL STRUCTURE OF THE RAT ANDROGEN RECEPTOR LIGAND BINDING DOMAIN T877A MUTANT COMPLEX WITH (3A-ALPHA-,4-ALPHA 7-ALPHA-,7A-ALPHA-)-3A,4,7,7A-TETRAHYDRO-2-(4-NITRO-1-NAPHTHALENYL)-4,7-ETHANO-1H-ISOINDOLE-1,3(2H)-DIONE.

Structural highlights

1xnn is a 1 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	Ar, Nr3c4 (Buffalo rat)
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 series of isoindoledione based compounds were identified as potent antagonists of the androgen receptor (AR). Co-crystallization of members of this family of inhibitors was successfully accomplished with the T877A AR LBD. A working model of how this class of compounds functions to antagonize the AR was created. Based on this model, it was proposed that expanding the bicyclic portion of the molecule should result in analogs which function as effective antagonists against a variety of AR isoforms. In contrast to what was predicted by the model, SAR around this new series was dictated by the aniline portion rather than the bicyclic portion of the molecule.

Structure based approach to the design of bicyclic-1H-isoindole-1,3(2H)-dione based androgen receptor antagonists.,Salvati ME, Balog A, Shan W, Wei DD, Pickering D, Attar RM, Geng J, Rizzo CA, Gottardis MM, Weinmann R, Krystek SR, Sack J, An Y, Kish K Bioorg Med Chem Lett. 2005 Jan 17;15(2):271-6. PMID:15603938^[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
↑ Salvati ME, Balog A, Shan W, Wei DD, Pickering D, Attar RM, Geng J, Rizzo CA, Gottardis MM, Weinmann R, Krystek SR, Sack J, An Y, Kish K. Structure based approach to the design of bicyclic-1H-isoindole-1,3(2H)-dione based androgen receptor antagonists. Bioorg Med Chem Lett. 2005 Jan 17;15(2):271-6. PMID:15603938 doi:10.1016/j.bmcl.2004.10.085

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/1xnn"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF THE RAT ANDROGEN RECEPTOR LIGAND BINDING DOMAIN T877A MUTANT COMPLEX WITH (3A-ALPHA-,4-ALPHA 7-ALPHA-,7A-ALPHA-)-3A,4,7,7A-TETRAHYDRO-2-(4-NITRO-1-NAPHTHALENYL)-4,7-ETHANO-1H-ISOINDOLE-1,3(2H)-DIONE.==
 <StructureSection load='1xnn' size='340' side='right' caption='[[1xnn]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HYQ:REL-(3AR,4S,7R,7AS)-3A,4,7,7A-TETRAHYDRO-2-(4-NITRO-1-NAPHTHALENYL)-4,7-ETHANO-1H-ISOINDOLE-1,3(2H)-DIONE'>HYQ</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ar, Nr3c4 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xnn OCA], [http://pdbe.org/1xnn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xnn RCSB], [http://www.ebi.ac.uk/pdbsum/1xnn PDBsum]</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=1xnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xnn OCA], [http://pdbe.org/1xnn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xnn RCSB], [http://www.ebi.ac.uk/pdbsum/1xnn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xnn ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xn/1xnn_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xn/1xnn_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1xnn

From Proteopedia

Revision as of 07:37, 18 April 2018

CRYSTAL STRUCTURE OF THE RAT ANDROGEN RECEPTOR LIGAND BINDING DOMAIN T877A MUTANT COMPLEX WITH (3A-ALPHA-,4-ALPHA 7-ALPHA-,7A-ALPHA-)-3A,4,7,7A-TETRAHYDRO-2-(4-NITRO-1-NAPHTHALENYL)-4,7-ETHANO-1H-ISOINDOLE-1,3(2H)-DIONE.

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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