3rll - Revision history

OCA at 12:28, 14 March 2024

OCA — Thu, 14 Mar 2024 12:28:49 GMT

←Older revision		Revision as of 12:28, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3rll' size='340' side='right'caption='[[3rll]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='3rll' size='340' side='right'caption='[[3rll]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3rll]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RLL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3rll]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RLL FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=RLL:(2S)-3~~-[~~(4-CYANONAPHTHALEN-1-YL)OXY]-N-~~[~~4-CYANO-3-(TRIFLUOROMETHYL)PHENYL~~]~~-2-HYDROXY-2-METHYLPROPANAMIDE'>RLL</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]] 1.7Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;'>~~[[~~3rlj\|3rlj~~]~~]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RLL:(2S)-3-[(4-CYANONAPHTHALEN-1-YL)OXY]-N-[4-CYANO-3-(TRIFLUOROMETHYL)PHENYL]-2-HYDROXY-2-METHYLPROPANAMIDE'>RLL</scene></td></tr>
-	~~<tr id='gene~~'>~~<td class="sblockLbl"><b>[[Gene\|Gene:]]~~</b>~~</td><td class="sblockDat">AR, DHTR, NR3C4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=3rll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rll OCA], [https://pdbe.org/3rll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rll RCSB], [https://www.ebi.ac.uk/pdbsum/3rll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rll 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=3rll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rll OCA], [https://pdbe.org/3rll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rll RCSB], [https://www.ebi.ac.uk/pdbsum/3rll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rll ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[https://omim.org/entry/300068 300068]]; previously known as testicular feminization syndrome (TFM). AIS is an X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.<ref>PMID:2594783</ref> <ref>PMID:8413310</ref> <ref>PMID:1775137</ref> <ref>PMID:16129672</ref> <ref>PMID:2082179</ref> <ref>PMID:1999491</ref> <ref>PMID:1609793</ref> <ref>PMID:1426313</ref> <ref>PMID:1487249</ref> <ref>PMID:1307250</ref> <ref>PMID:1569163</ref> <ref>PMID:1464650</ref> <ref>PMID:1430233</ref> <ref>PMID:1316540</ref> <ref>PMID:1480178</ref> <ref>PMID:8224266</ref> <ref>PMID:8103398</ref> <ref>PMID:8281140</ref> <ref>PMID:8325950</ref> <ref>PMID:8096390</ref> <ref>PMID:8446106</ref> [:]<ref>PMID:8162033</ref> <ref>PMID:7981687</ref> <ref>PMID:7981689</ref> <ref>PMID:7962294</ref> <ref>PMID:8040309</ref> <ref>PMID:7929841</ref> <ref>PMID:7993455</ref> <ref>PMID:7970939</ref> <ref>PMID:8830623</ref> <ref>PMID:7641413</ref> <ref>PMID:7671849</ref> <ref>PMID:7633398</ref> <ref>PMID:7537149</ref> <ref>PMID:7581399</ref> <ref>PMID:8723113</ref> <ref>PMID:9039340</ref> <ref>PMID:9001799</ref> <ref>PMID:8626869</ref> <ref>PMID:8768864</ref> <ref>PMID:8918984</ref> <ref>PMID:8683794</ref> <ref>PMID:8647313</ref> <ref>PMID:8809734</ref> <ref>PMID:9106550</ref> <ref>PMID:9160185</ref> <ref>PMID:9007482</ref> <ref>PMID:8990010</ref> <ref>PMID:9255042</ref> <ref>PMID:9252933</ref> <ref>PMID:9328206</ref> <ref>PMID:9302173</ref> <ref>PMID:9544375</ref> <ref>PMID:9698822</ref> <ref>PMID:9788719</ref> <ref>PMID:9610419</ref> <ref>PMID:9856504</ref> <ref>PMID:9554754</ref> [:]<ref>PMID:9851768</ref> <ref>PMID:9627582</ref> <ref>PMID:10571951</ref> <ref>PMID:10221692</ref> <ref>PMID:10404311</ref> <ref>PMID:10022458</ref> <ref>PMID:10221770</ref> <ref>PMID:10590024</ref> <ref>PMID:10458483</ref> <ref>PMID:10690872</ref> <ref>PMID:11587068</ref> <ref>PMID:11744994</ref> <ref>PMID:16595706</ref> Defects in AR are the cause of spinal and bulbar muscular atrophy X-linked type 1 (SMAX1) [MIM:[https://omim.org/entry/313200 313200]]; also known as Kennedy disease. SMAX1 is an X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. Note=Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:15851746</ref> Note=Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor. Defects in AR are the cause of androgen insensitivity syndrome partial (PAIS) [MIM:[https://omim.org/entry/312300 312300]]; also known as Reifenstein syndrome. PAIS is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations.	+	[https://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[https://omim.org/entry/300068 300068]; previously known as testicular feminization syndrome (TFM). AIS is an X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.<ref>PMID:2594783</ref> <ref>PMID:8413310</ref> <ref>PMID:1775137</ref> <ref>PMID:16129672</ref> <ref>PMID:2082179</ref> <ref>PMID:1999491</ref> <ref>PMID:1609793</ref> <ref>PMID:1426313</ref> <ref>PMID:1487249</ref> <ref>PMID:1307250</ref> <ref>PMID:1569163</ref> <ref>PMID:1464650</ref> <ref>PMID:1430233</ref> <ref>PMID:1316540</ref> <ref>PMID:1480178</ref> <ref>PMID:8224266</ref> <ref>PMID:8103398</ref> <ref>PMID:8281140</ref> <ref>PMID:8325950</ref> <ref>PMID:8096390</ref> <ref>PMID:8446106</ref> [:]<ref>PMID:8162033</ref> <ref>PMID:7981687</ref> <ref>PMID:7981689</ref> <ref>PMID:7962294</ref> <ref>PMID:8040309</ref> <ref>PMID:7929841</ref> <ref>PMID:7993455</ref> <ref>PMID:7970939</ref> <ref>PMID:8830623</ref> <ref>PMID:7641413</ref> <ref>PMID:7671849</ref> <ref>PMID:7633398</ref> <ref>PMID:7537149</ref> <ref>PMID:7581399</ref> <ref>PMID:8723113</ref> <ref>PMID:9039340</ref> <ref>PMID:9001799</ref> <ref>PMID:8626869</ref> <ref>PMID:8768864</ref> <ref>PMID:8918984</ref> <ref>PMID:8683794</ref> <ref>PMID:8647313</ref> <ref>PMID:8809734</ref> <ref>PMID:9106550</ref> <ref>PMID:9160185</ref> <ref>PMID:9007482</ref> <ref>PMID:8990010</ref> <ref>PMID:9255042</ref> <ref>PMID:9252933</ref> <ref>PMID:9328206</ref> <ref>PMID:9302173</ref> <ref>PMID:9544375</ref> <ref>PMID:9698822</ref> <ref>PMID:9788719</ref> <ref>PMID:9610419</ref> <ref>PMID:9856504</ref> <ref>PMID:9554754</ref> [:]<ref>PMID:9851768</ref> <ref>PMID:9627582</ref> <ref>PMID:10571951</ref> <ref>PMID:10221692</ref> <ref>PMID:10404311</ref> <ref>PMID:10022458</ref> <ref>PMID:10221770</ref> <ref>PMID:10590024</ref> <ref>PMID:10458483</ref> <ref>PMID:10690872</ref> <ref>PMID:11587068</ref> <ref>PMID:11744994</ref> <ref>PMID:16595706</ref> Defects in AR are the cause of spinal and bulbar muscular atrophy X-linked type 1 (SMAX1) [MIM:[https://omim.org/entry/313200 313200]; also known as Kennedy disease. SMAX1 is an X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. Note=Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:15851746</ref> Note=Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor. Defects in AR are the cause of androgen insensitivity syndrome partial (PAIS) [MIM:[https://omim.org/entry/312300 312300]; also known as Reifenstein syndrome. PAIS is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] 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.<ref>PMID:14664718</ref> <ref>PMID:18084323</ref> <ref>PMID:19345326</ref> <ref>PMID:20980437</ref> <ref>PMID:15563469</ref> <ref>PMID:17591767</ref> <ref>PMID:17911242</ref>	+	[https://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN] 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.<ref>PMID:14664718</ref> <ref>PMID:18084323</ref> <ref>PMID:19345326</ref> <ref>PMID:20980437</ref> <ref>PMID:15563469</ref> <ref>PMID:17591767</ref> <ref>PMID:17911242</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Several new androgen receptor antagonists were synthesized and found to have varying activities across typically anti-androgen resistant mutants (Thr877-->Ala and Trp741-->Leu) and markedly improved potency over previously reported pan-antagonists. X-ray crystallography of a new anti-androgen in an androgen receptor mutant (Thr877-->Ala) shows that the receptor can accommodate the added bulk presented by phenyl to naphthyl substitution, casting doubt on previous reports of predicted binding orientation and the causes of antagonism in bulky-B-ring antagonists.	+
-		+
-	Unexpected Binding Orientation of Bulky-B-Ring Anti-Androgens and Implications for Future Drug Targets.,Duke CB, Jones A, Bohl CE, Dalton JT, Miller DD J Med Chem. 2011 Apr 20. PMID:21506597<ref>PMID:21506597</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3rll" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 29:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bohl~~, C E~~]]	+	[[Category: Bohl CE]]
-	[[Category: Dalton~~, J T~~]]	+	[[Category: Dalton JT]]
-	[[Category: Duke~~, C B~~]]	+	[[Category: Duke CB]]
-	[[Category: Jones, A]]	+	[[Category: Jones A]]
-	[[Category: Miller~~, D D]]~~	+	[[Category: Miller DD]]
-	~~[[Category: Dht]]~~	+
-	~~[[Category: Steroid receptor]]~~	+
-	~~[[Category: Testosterone]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 10:16, 22 June 2022

OCA — Wed, 22 Jun 2022 10:16:02 GMT

←Older revision		Revision as of 10:16, 22 June 2022
Line 1:		Line 1:

	==Crystal structure of the T877A androgen receptor ligand binding domain in complex with (S)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanonaphthalen-1-yloxy)-2-hydroxy-2-methylpropanamide==		==Crystal structure of the T877A androgen receptor ligand binding domain in complex with (S)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanonaphthalen-1-yloxy)-2-hydroxy-2-methylpropanamide==
-	<StructureSection load='3rll' size='340' side='right' caption='[[3rll]], [[Resolution\|resolution]] 1.70Å' scene=''>	+	<StructureSection load='3rll' size='340' side='right'caption='[[3rll]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3rll]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RLL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3RLL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3rll]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RLL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RLL:(2S)-3-[(4-CYANONAPHTHALEN-1-YL)OXY]-N-[4-CYANO-3-(TRIFLUOROMETHYL)PHENYL]-2-HYDROXY-2-METHYLPROPANAMIDE'>RLL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RLL:(2S)-3-[(4-CYANONAPHTHALEN-1-YL)OXY]-N-[4-CYANO-3-(TRIFLUOROMETHYL)PHENYL]-2-HYDROXY-2-METHYLPROPANAMIDE'>RLL</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3rlj\|3rlj]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3rlj\|3rlj]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AR, DHTR, NR3C4 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AR, DHTR, NR3C4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3rll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rll OCA], [~~http~~://pdbe.org/3rll PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3rll RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3rll PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3rll 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=3rll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rll OCA], [https://pdbe.org/3rll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rll RCSB], [https://www.ebi.ac.uk/pdbsum/3rll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rll ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[~~http~~://omim.org/entry/300068 300068]]; previously known as testicular feminization syndrome (TFM). AIS is an X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.<ref>PMID:2594783</ref> <ref>PMID:8413310</ref> <ref>PMID:1775137</ref> <ref>PMID:16129672</ref> <ref>PMID:2082179</ref> <ref>PMID:1999491</ref> <ref>PMID:1609793</ref> <ref>PMID:1426313</ref> <ref>PMID:1487249</ref> <ref>PMID:1307250</ref> <ref>PMID:1569163</ref> <ref>PMID:1464650</ref> <ref>PMID:1430233</ref> <ref>PMID:1316540</ref> <ref>PMID:1480178</ref> <ref>PMID:8224266</ref> <ref>PMID:8103398</ref> <ref>PMID:8281140</ref> <ref>PMID:8325950</ref> <ref>PMID:8096390</ref> <ref>PMID:8446106</ref> [:]<ref>PMID:8162033</ref> <ref>PMID:7981687</ref> <ref>PMID:7981689</ref> <ref>PMID:7962294</ref> <ref>PMID:8040309</ref> <ref>PMID:7929841</ref> <ref>PMID:7993455</ref> <ref>PMID:7970939</ref> <ref>PMID:8830623</ref> <ref>PMID:7641413</ref> <ref>PMID:7671849</ref> <ref>PMID:7633398</ref> <ref>PMID:7537149</ref> <ref>PMID:7581399</ref> <ref>PMID:8723113</ref> <ref>PMID:9039340</ref> <ref>PMID:9001799</ref> <ref>PMID:8626869</ref> <ref>PMID:8768864</ref> <ref>PMID:8918984</ref> <ref>PMID:8683794</ref> <ref>PMID:8647313</ref> <ref>PMID:8809734</ref> <ref>PMID:9106550</ref> <ref>PMID:9160185</ref> <ref>PMID:9007482</ref> <ref>PMID:8990010</ref> <ref>PMID:9255042</ref> <ref>PMID:9252933</ref> <ref>PMID:9328206</ref> <ref>PMID:9302173</ref> <ref>PMID:9544375</ref> <ref>PMID:9698822</ref> <ref>PMID:9788719</ref> <ref>PMID:9610419</ref> <ref>PMID:9856504</ref> <ref>PMID:9554754</ref> [:]<ref>PMID:9851768</ref> <ref>PMID:9627582</ref> <ref>PMID:10571951</ref> <ref>PMID:10221692</ref> <ref>PMID:10404311</ref> <ref>PMID:10022458</ref> <ref>PMID:10221770</ref> <ref>PMID:10590024</ref> <ref>PMID:10458483</ref> <ref>PMID:10690872</ref> <ref>PMID:11587068</ref> <ref>PMID:11744994</ref> <ref>PMID:16595706</ref> Defects in AR are the cause of spinal and bulbar muscular atrophy X-linked type 1 (SMAX1) [MIM:[~~http~~://omim.org/entry/313200 313200]]; also known as Kennedy disease. SMAX1 is an X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. Note=Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:15851746</ref> Note=Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor. Defects in AR are the cause of androgen insensitivity syndrome partial (PAIS) [MIM:[~~http~~://omim.org/entry/312300 312300]]; also known as Reifenstein syndrome. PAIS is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations.	+	[[https://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[https://omim.org/entry/300068 300068]]; previously known as testicular feminization syndrome (TFM). AIS is an X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.<ref>PMID:2594783</ref> <ref>PMID:8413310</ref> <ref>PMID:1775137</ref> <ref>PMID:16129672</ref> <ref>PMID:2082179</ref> <ref>PMID:1999491</ref> <ref>PMID:1609793</ref> <ref>PMID:1426313</ref> <ref>PMID:1487249</ref> <ref>PMID:1307250</ref> <ref>PMID:1569163</ref> <ref>PMID:1464650</ref> <ref>PMID:1430233</ref> <ref>PMID:1316540</ref> <ref>PMID:1480178</ref> <ref>PMID:8224266</ref> <ref>PMID:8103398</ref> <ref>PMID:8281140</ref> <ref>PMID:8325950</ref> <ref>PMID:8096390</ref> <ref>PMID:8446106</ref> [:]<ref>PMID:8162033</ref> <ref>PMID:7981687</ref> <ref>PMID:7981689</ref> <ref>PMID:7962294</ref> <ref>PMID:8040309</ref> <ref>PMID:7929841</ref> <ref>PMID:7993455</ref> <ref>PMID:7970939</ref> <ref>PMID:8830623</ref> <ref>PMID:7641413</ref> <ref>PMID:7671849</ref> <ref>PMID:7633398</ref> <ref>PMID:7537149</ref> <ref>PMID:7581399</ref> <ref>PMID:8723113</ref> <ref>PMID:9039340</ref> <ref>PMID:9001799</ref> <ref>PMID:8626869</ref> <ref>PMID:8768864</ref> <ref>PMID:8918984</ref> <ref>PMID:8683794</ref> <ref>PMID:8647313</ref> <ref>PMID:8809734</ref> <ref>PMID:9106550</ref> <ref>PMID:9160185</ref> <ref>PMID:9007482</ref> <ref>PMID:8990010</ref> <ref>PMID:9255042</ref> <ref>PMID:9252933</ref> <ref>PMID:9328206</ref> <ref>PMID:9302173</ref> <ref>PMID:9544375</ref> <ref>PMID:9698822</ref> <ref>PMID:9788719</ref> <ref>PMID:9610419</ref> <ref>PMID:9856504</ref> <ref>PMID:9554754</ref> [:]<ref>PMID:9851768</ref> <ref>PMID:9627582</ref> <ref>PMID:10571951</ref> <ref>PMID:10221692</ref> <ref>PMID:10404311</ref> <ref>PMID:10022458</ref> <ref>PMID:10221770</ref> <ref>PMID:10590024</ref> <ref>PMID:10458483</ref> <ref>PMID:10690872</ref> <ref>PMID:11587068</ref> <ref>PMID:11744994</ref> <ref>PMID:16595706</ref> Defects in AR are the cause of spinal and bulbar muscular atrophy X-linked type 1 (SMAX1) [MIM:[https://omim.org/entry/313200 313200]]; also known as Kennedy disease. SMAX1 is an X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. Note=Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:15851746</ref> Note=Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor. Defects in AR are the cause of androgen insensitivity syndrome partial (PAIS) [MIM:[https://omim.org/entry/312300 312300]]; also known as Reifenstein syndrome. PAIS is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations.
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] 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.<ref>PMID:14664718</ref> <ref>PMID:18084323</ref> <ref>PMID:19345326</ref> <ref>PMID:20980437</ref> <ref>PMID:15563469</ref> <ref>PMID:17591767</ref> <ref>PMID:17911242</ref>	+	[[https://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] 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.<ref>PMID:14664718</ref> <ref>PMID:18084323</ref> <ref>PMID:19345326</ref> <ref>PMID:20980437</ref> <ref>PMID:15563469</ref> <ref>PMID:17591767</ref> <ref>PMID:17911242</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 24:

	==See Also==		==See Also==
-	*[[Androgen receptor\|Androgen receptor]]	+	*[[Androgen receptor 3D structures\|Androgen receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 30:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bohl, C E]]		[[Category: Bohl, C E]]
	[[Category: Dalton, J T]]		[[Category: Dalton, J T]]

OCA at 14:30, 4 August 2016

OCA — Thu, 04 Aug 2016 14:30:01 GMT

←Older revision		Revision as of 14:30, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of the T877A androgen receptor ligand binding domain in complex with (S)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanonaphthalen-1-yloxy)-2-hydroxy-2-methylpropanamide==		==Crystal structure of the T877A androgen receptor ligand binding domain in complex with (S)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanonaphthalen-1-yloxy)-2-hydroxy-2-methylpropanamide==
	<StructureSection load='3rll' size='340' side='right' caption='[[3rll]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='3rll' size='340' side='right' caption='[[3rll]], [[Resolution\|resolution]] 1.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3rll]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RLL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RLL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3rll]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RLL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RLL FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RLL:(2S)-3-[(4-CYANONAPHTHALEN-1-YL)OXY]-N-[4-CYANO-3-(TRIFLUOROMETHYL)PHENYL]-2-HYDROXY-2-METHYLPROPANAMIDE'>RLL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RLL:(2S)-3-[(4-CYANONAPHTHALEN-1-YL)OXY]-N-[4-CYANO-3-(TRIFLUOROMETHYL)PHENYL]-2-HYDROXY-2-METHYLPROPANAMIDE'>RLL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3rlj\|3rlj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3rlj\|3rlj]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AR, DHTR, NR3C4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AR, DHTR, NR3C4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3rll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rll OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rll RCSB], [http://www.ebi.ac.uk/pdbsum/3rll 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=3rll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rll OCA], [http://pdbe.org/3rll PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rll RCSB], [http://www.ebi.ac.uk/pdbsum/3rll PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rll ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3rll" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Bohl, C E]]		[[Category: Bohl, C E]]
	[[Category: Dalton, J T]]		[[Category: Dalton, J T]]

OCA at 10:07, 19 December 2014

OCA — Fri, 19 Dec 2014 10:07:12 GMT

←Older revision		Revision as of 10:07, 19 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3rll\| PDB=3rll \| SCENE= }}~~	+	==Crystal structure of the T877A androgen receptor ligand binding domain in complex with (S)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanonaphthalen-1-yloxy)-2-hydroxy-2-methylpropanamide==
-	===Crystal structure of the T877A androgen receptor ligand binding domain in complex with (S)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanonaphthalen-1-yloxy)-2-hydroxy-2-methylpropanamide===	+	<StructureSection load='3rll' size='340' side='right' caption='[[3rll]], [[Resolution\|resolution]] 1.70Å' scene=''>
-	~~{{ABSTRACT_PUBMED_21506597}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3rll]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RLL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RLL FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RLL:(2S)-3-[(4-CYANONAPHTHALEN-1-YL)OXY]-N-[4-CYANO-3-(TRIFLUOROMETHYL)PHENYL]-2-HYDROXY-2-METHYLPROPANAMIDE'>RLL</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3rlj\|3rlj]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AR, DHTR, NR3C4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3rll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rll OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rll RCSB], [http://www.ebi.ac.uk/pdbsum/3rll PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[http://omim.org/entry/300068 300068]]; previously known as testicular feminization syndrome (TFM). AIS is an X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.<ref>PMID:2594783</ref> <ref>PMID:8413310</ref> <ref>PMID:1775137</ref> <ref>PMID:16129672</ref> <ref>PMID:2082179</ref> <ref>PMID:1999491</ref> <ref>PMID:1609793</ref> <ref>PMID:1426313</ref> <ref>PMID:1487249</ref> <ref>PMID:1307250</ref> <ref>PMID:1569163</ref> <ref>PMID:1464650</ref> <ref>PMID:1430233</ref> <ref>PMID:1316540</ref> <ref>PMID:1480178</ref> <ref>PMID:8224266</ref> <ref>PMID:8103398</ref> <ref>PMID:8281140</ref> <ref>PMID:8325950</ref> <ref>PMID:8096390</ref> <ref>PMID:8446106</ref> [:]<ref>PMID:8162033</ref> <ref>PMID:7981687</ref> <ref>PMID:7981689</ref> <ref>PMID:7962294</ref> <ref>PMID:8040309</ref> <ref>PMID:7929841</ref> <ref>PMID:7993455</ref> <ref>PMID:7970939</ref> <ref>PMID:8830623</ref> <ref>PMID:7641413</ref> <ref>PMID:7671849</ref> <ref>PMID:7633398</ref> <ref>PMID:7537149</ref> <ref>PMID:7581399</ref> <ref>PMID:8723113</ref> <ref>PMID:9039340</ref> <ref>PMID:9001799</ref> <ref>PMID:8626869</ref> <ref>PMID:8768864</ref> <ref>PMID:8918984</ref> <ref>PMID:8683794</ref> <ref>PMID:8647313</ref> <ref>PMID:8809734</ref> <ref>PMID:9106550</ref> <ref>PMID:9160185</ref> <ref>PMID:9007482</ref> <ref>PMID:8990010</ref> <ref>PMID:9255042</ref> <ref>PMID:9252933</ref> <ref>PMID:9328206</ref> <ref>PMID:9302173</ref> <ref>PMID:9544375</ref> <ref>PMID:9698822</ref> <ref>PMID:9788719</ref> <ref>PMID:9610419</ref> <ref>PMID:9856504</ref> <ref>PMID:9554754</ref> [:]<ref>PMID:9851768</ref> <ref>PMID:9627582</ref> <ref>PMID:10571951</ref> <ref>PMID:10221692</ref> <ref>PMID:10404311</ref> <ref>PMID:10022458</ref> <ref>PMID:10221770</ref> <ref>PMID:10590024</ref> <ref>PMID:10458483</ref> <ref>PMID:10690872</ref> <ref>PMID:11587068</ref> <ref>PMID:11744994</ref> <ref>PMID:16595706</ref> Defects in AR are the cause of spinal and bulbar muscular atrophy X-linked type 1 (SMAX1) [MIM:[http://omim.org/entry/313200 313200]]; also known as Kennedy disease. SMAX1 is an X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. Note=Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:15851746</ref> Note=Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor. Defects in AR are the cause of androgen insensitivity syndrome partial (PAIS) [MIM:[http://omim.org/entry/312300 312300]]; also known as Reifenstein syndrome. PAIS is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] 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.<ref>PMID:14664718</ref> <ref>PMID:18084323</ref> <ref>PMID:19345326</ref> <ref>PMID:20980437</ref> <ref>PMID:15563469</ref> <ref>PMID:17591767</ref> <ref>PMID:17911242</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Several new androgen receptor antagonists were synthesized and found to have varying activities across typically anti-androgen resistant mutants (Thr877-->Ala and Trp741-->Leu) and markedly improved potency over previously reported pan-antagonists. X-ray crystallography of a new anti-androgen in an androgen receptor mutant (Thr877-->Ala) shows that the receptor can accommodate the added bulk presented by phenyl to naphthyl substitution, casting doubt on previous reports of predicted binding orientation and the causes of antagonism in bulky-B-ring antagonists.

-	~~==Disease==~~	+	Unexpected Binding Orientation of Bulky-B-Ring Anti-Androgens and Implications for Future Drug Targets.,Duke CB, Jones A, Bohl CE, Dalton JT, Miller DD J Med Chem. 2011 Apr 20. PMID:21506597<ref>PMID:21506597</ref>
-	~~[[http://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects in AR are the cause~~ of ~~androgen insensitivity syndrome (AIS) [MIM:[http://omim.org/entry/300068 300068]]; previously known as testicular feminization syndrome (TFM). AIS is an X~~-~~linked recessive form of pseudohermaphroditism due end~~-~~organ resistance to androgen~~. ~~Affected males have female external genitalia~~, ~~female breast development~~, ~~blind vagina~~, ~~absent uterus and female adnexa, and abdominal or inguinal testes~~, ~~despite a normal 46~~,~~XY karyotype~~.~~<ref>~~PMID:~~2594783</ref>~~<ref>PMID:~~8413310~~</ref><ref>PMID:1775137</ref><ref>PMID:16129672</ref><ref>PMID:2082179</ref><ref>PMID:1999491</ref><ref>PMID:1609793</ref><ref>PMID:1426313</ref><ref>PMID:1487249</ref><ref>PMID:1307250</ref><ref>PMID:1569163</ref><ref>PMID:1464650</ref><ref>PMID:1430233</ref><ref>PMID:1316540</ref><ref>PMID:1480178</ref><ref>PMID:8224266</ref><ref>PMID:8103398</ref><ref>PMID:8281140</ref><ref>PMID:8325950</ref><ref>PMID:8096390</ref><ref>PMID:8446106</ref>[:]<ref>PMID:8162033</ref><ref>PMID:7981687</ref><ref>PMID:7981689</ref><ref>PMID:7962294</ref><ref>PMID:8040309</ref><ref>PMID:7929841</ref><ref>PMID:7993455</ref><ref>PMID:7970939</ref><ref>PMID:8830623</ref><ref>PMID:7641413</ref><ref>PMID:7671849</ref><ref>PMID:7633398</ref><ref>PMID:7537149</ref><ref>PMID:7581399</ref><ref>PMID:8723113</ref><ref>PMID:9039340</ref><ref>PMID:9001799</ref><ref>PMID:8626869</ref><ref>PMID:8768864</ref><ref>PMID:8918984</ref><ref>PMID:8683794</ref><ref>PMID:8647313</ref><ref>PMID:8809734</ref><ref>PMID:9106550</ref><ref>PMID:9160185</ref><ref>PMID:9007482</ref><ref>PMID:8990010</ref><ref>PMID:9255042</ref><ref>PMID:9252933</ref><ref>PMID:9328206</ref><ref>PMID:9302173</ref><ref>PMID:9544375</ref><ref>PMID:9698822</ref><ref>PMID:9788719</ref><ref>PMID:9610419</ref><ref>PMID:9856504</ref><ref>PMID:9554754</ref>[:]<ref>PMID:9851768</ref><ref>PMID:9627582</ref><ref>PMID:10571951</ref><ref>PMID:10221692</ref><ref>PMID:10404311</ref><ref>PMID:10022458</ref><ref>PMID:10221770</ref><ref>PMID:10590024</ref><ref>PMID:10458483</ref><ref>PMID:10690872</ref><ref>PMID:11587068</ref><ref>PMID:11744994</ref><ref>PMID:16595706</ref> Defects in AR are the cause of spinal and bulbar muscular atrophy X-linked type 1 (SMAX1) [MIM:[http://omim.org/entry/313200 313200]]; also known as Kennedy disease. SMAX1 is an X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. Note=Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:15851746</ref> Note=Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor. Defects in AR are the cause of androgen insensitivity syndrome partial (PAIS) [MIM:[http://omim.org/entry/312300 312300]]; also known as Reifenstein syndrome. PAIS is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations.	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www~~.~~uniprot~~.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] 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.<~~ref~~>~~PMID:14664718</ref><ref>PMID:18084323</ref><ref>PMID:19345326</ref><ref>PMID:20980437</ref><ref>PMID:15563469</ref><ref>PMID:17591767</ref><ref>PMID:17911242~~</~~ref~~>	+	</div>

-	==~~About this Structure~~==	+	==See Also==
-	[[~~3rll~~]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RLL OCA].	+	*[[Androgen receptor\|Androgen receptor]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:021506597</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Bohl, C E.]]	+	[[Category: Bohl, C E]]
-	[[Category: Dalton, J T.]]	+	[[Category: Dalton, J T]]
-	[[Category: Duke, C B.]]	+	[[Category: Duke, C B]]
-	[[Category: Jones, A.]]	+	[[Category: Jones, A]]
-	[[Category: Miller, D D.]]	+	[[Category: Miller, D D]]
	[[Category: Dht]]		[[Category: Dht]]
	[[Category: Steroid receptor]]		[[Category: Steroid receptor]]
	[[Category: Testosterone]]		[[Category: Testosterone]]
	[[Category: Transcription]]		[[Category: Transcription]]

OCA at 20:24, 24 March 2013

OCA — Sun, 24 Mar 2013 20:24:55 GMT

←Older revision		Revision as of 20:24, 24 March 2013
Line 1:		Line 1:
-	[[Image:3rll.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3rll", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3rll\| PDB=3rll \| SCENE= }}		{{STRUCTURE_3rll\| PDB=3rll \| SCENE= }}
-
	===Crystal structure of the T877A androgen receptor ligand binding domain in complex with (S)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanonaphthalen-1-yloxy)-2-hydroxy-2-methylpropanamide===		===Crystal structure of the T877A androgen receptor ligand binding domain in complex with (S)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanonaphthalen-1-yloxy)-2-hydroxy-2-methylpropanamide===
		+	{{ABSTRACT_PUBMED_21506597}}

		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[http://omim.org/entry/300068 300068]]; previously known as testicular feminization syndrome (TFM). AIS is an X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.<ref>PMID:2594783</ref><ref>PMID:8413310</ref><ref>PMID:1775137</ref><ref>PMID:16129672</ref><ref>PMID:2082179</ref><ref>PMID:1999491</ref><ref>PMID:1609793</ref><ref>PMID:1426313</ref><ref>PMID:1487249</ref><ref>PMID:1307250</ref><ref>PMID:1569163</ref><ref>PMID:1464650</ref><ref>PMID:1430233</ref><ref>PMID:1316540</ref><ref>PMID:1480178</ref><ref>PMID:8224266</ref><ref>PMID:8103398</ref><ref>PMID:8281140</ref><ref>PMID:8325950</ref><ref>PMID:8096390</ref><ref>PMID:8446106</ref>[:]<ref>PMID:8162033</ref><ref>PMID:7981687</ref><ref>PMID:7981689</ref><ref>PMID:7962294</ref><ref>PMID:8040309</ref><ref>PMID:7929841</ref><ref>PMID:7993455</ref><ref>PMID:7970939</ref><ref>PMID:8830623</ref><ref>PMID:7641413</ref><ref>PMID:7671849</ref><ref>PMID:7633398</ref><ref>PMID:7537149</ref><ref>PMID:7581399</ref><ref>PMID:8723113</ref><ref>PMID:9039340</ref><ref>PMID:9001799</ref><ref>PMID:8626869</ref><ref>PMID:8768864</ref><ref>PMID:8918984</ref><ref>PMID:8683794</ref><ref>PMID:8647313</ref><ref>PMID:8809734</ref><ref>PMID:9106550</ref><ref>PMID:9160185</ref><ref>PMID:9007482</ref><ref>PMID:8990010</ref><ref>PMID:9255042</ref><ref>PMID:9252933</ref><ref>PMID:9328206</ref><ref>PMID:9302173</ref><ref>PMID:9544375</ref><ref>PMID:9698822</ref><ref>PMID:9788719</ref><ref>PMID:9610419</ref><ref>PMID:9856504</ref><ref>PMID:9554754</ref>[:]<ref>PMID:9851768</ref><ref>PMID:9627582</ref><ref>PMID:10571951</ref><ref>PMID:10221692</ref><ref>PMID:10404311</ref><ref>PMID:10022458</ref><ref>PMID:10221770</ref><ref>PMID:10590024</ref><ref>PMID:10458483</ref><ref>PMID:10690872</ref><ref>PMID:11587068</ref><ref>PMID:11744994</ref><ref>PMID:16595706</ref> Defects in AR are the cause of spinal and bulbar muscular atrophy X-linked type 1 (SMAX1) [MIM:[http://omim.org/entry/313200 313200]]; also known as Kennedy disease. SMAX1 is an X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. Note=Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.<ref>PMID:15851746</ref> Note=Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor. Defects in AR are the cause of androgen insensitivity syndrome partial (PAIS) [MIM:[http://omim.org/entry/312300 312300]]; also known as Reifenstein syndrome. PAIS is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations.

-	~~<!--~~	+	==Function==
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_21506597}}, adds the Publication Abstract to the page~~	+	[[http://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] 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.<ref>PMID:14664718</ref><ref>PMID:18084323</ref><ref>PMID:19345326</ref><ref>PMID:20980437</ref><ref>PMID:15563469</ref><ref>PMID:17591767</ref><ref>PMID:17911242</ref>
-	~~(as it appears on PubMed at~~ http://www.~~pubmed~~.~~gov), where 21506597~~ is ~~the PubMed ID number~~.	+
-	-->	+
-	~~{{ABSTRACT_PUBMED_21506597}}~~	+

	==About this Structure==		==About this Structure==
Line 22:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:021506597</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021506597</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Bohl, C E.]]		[[Category: Bohl, C E.]]

OCA at 05:15, 15 June 2011

OCA — Wed, 15 Jun 2011 05:15:40 GMT

←Older revision		Revision as of 05:15, 15 June 2011
Line 1:		Line 1:
-	[[Image:3rll.~~jpg~~\|left\|200px]]	+	[[Image:3rll.png\|left\|200px]]

	<!--		<!--
Line 29:		Line 29:
	[[Category: Jones, A.]]		[[Category: Jones, A.]]
	[[Category: Miller, D D.]]		[[Category: Miller, D D.]]
		+	[[Category: Dht]]
		+	[[Category: Steroid receptor]]
		+	[[Category: Testosterone]]
		+	[[Category: Transcription]]

OCA at 06:46, 4 May 2011

OCA — Wed, 04 May 2011 06:46:52 GMT

←Older revision		Revision as of 06:46, 4 May 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3rll.jpg\|left\|200px]]

-	The ~~entry 3rll~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3rll", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3rll\| PDB=3rll \| SCENE= }}

-	~~Authors: Bohl, C.E., Duke, C.B., Jones, A, Dalton, J.T., Miller, D.D.~~	+	===Crystal structure of the T877A androgen receptor ligand binding domain in complex with (S)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanonaphthalen-1-yloxy)-2-hydroxy-2-methylpropanamide===

-	~~Description: Crystal structure of the T877A androgen receptor ligand binding domain in complex with (S)~~-N-(~~4-Cyano-3-(trifluoromethyl)phenyl~~)-~~3-(4-cyanonaphthalen~~-1-~~yloxy)-2-hydroxy-2-methylpropanamide~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21506597}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21506597 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21506597}}
		+
		+	==About this Structure==
		+	[[3rll]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RLL OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021506597</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Bohl, C E.]]
		+	[[Category: Dalton, J T.]]
		+	[[Category: Duke, C B.]]
		+	[[Category: Jones, A.]]
		+	[[Category: Miller, D D.]]

OCA: Protected "3rll" [edit=sysop:move=sysop]

OCA — Wed, 27 Apr 2011 06:58:56 GMT

Protected "3rll" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:58, 27 April 2011

OCA: New page: '''Unreleased structure''' The entry 3rll is ON HOLD Authors: Bohl, C.E., Duke, C.B., Jones, A, Dalton, J.T., Miller, D.D. Description: Crystal structure of the T877A androgen receptor...

OCA — Wed, 27 Apr 2011 06:58:56 GMT

New page: '''Unreleased structure''' The entry 3rll is ON HOLD Authors: Bohl, C.E., Duke, C.B., Jones, A, Dalton, J.T., Miller, D.D. Description: Crystal structure of the T877A androgen receptor...

New page

'''Unreleased structure'''

The entry 3rll is ON HOLD

Authors: Bohl, C.E., Duke, C.B., Jones, A, Dalton, J.T., Miller, D.D.

Description: Crystal structure of the T877A androgen receptor ligand binding domain in complex with (S)-N-(4-Cyano-3-(trifluoromethyl)phenyl)-3-(4-cyanonaphthalen-1-yloxy)-2-hydroxy-2-methylpropanamide