4e2j - Revision history

OCA at 14:50, 14 March 2024

2024-03-14T14:50:20Z

← Older revision		Revision as of 14:50, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e2j]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E2J FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e2j]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E2J FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MOF:MOMETASONE+FUROATE'>MOF</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]] 2.5Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MOF:MOMETASONE+FUROATE'>MOF</scene></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=4e2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e2j OCA], [https://pdbe.org/4e2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e2j RCSB], [https://www.ebi.ac.uk/pdbsum/4e2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e2j 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=4e2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e2j OCA], [https://pdbe.org/4e2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e2j RCSB], [https://www.ebi.ac.uk/pdbsum/4e2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e2j ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.		[https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>		[https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Steroid receptors (SRs) are the largest family of metazoan transcription factors and control genes involved in development, endocrine signaling, reproduction, immunity, and cancer. The entire hormone receptor system is driven by a molecular switch triggered by the binding of small lipophilic ligands. This makes the SRs ideal pharmaceutical targets, yet even the best clinically approved synthetic steroidal agonists are prone to cross-reactivity and off-target pharmacology. The mechanism underlying this promiscuity is derived from the fact that SRs share common structural features derived from their evolutionary relationship. More often than not, rational attempts to probe SR drug selectivity via mutagenesis fail even when high quality structural and functional data are available due to the fact that important mutations often result in nonfunctional receptors. This highlights the fact that SRs suffer from instability, preventing in-depth mutational analysis and hampering crystallization of key receptor-ligand complexes. We have taken a unique approach to address this problem by using a resurrected ancestral protein to determine the structure of a previously intractable complex and identified the structural mechanisms that confer activation and selectivity for a widely used glucocorticoid, mometasone furoate. Moreover, we have identified a single residue located outside of the ligand-binding pocket that controls mometasone furoate antagonism versus agonism in the human mineralocorticoid receptor.

	Deciphering Modern Glucocorticoid Cross-pharmacology Using Ancestral Corticosteroid Receptors.,Kohn JA, Deshpande K, Ortlund EA J Biol Chem. 2012 May 11;287(20):16267-75. Epub 2012 Mar 21. PMID:22437833<ref>PMID:22437833</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4e2j" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==

OCA at 06:46, 28 September 2022

2022-09-28T06:46:23Z

← Older revision		Revision as of 06:46, 28 September 2022
Line 3:		Line 3:
	<StructureSection load='4e2j' size='340' side='right'caption='[[4e2j]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4e2j' size='340' side='right'caption='[[4e2j]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e2j]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Synthetic_construct_sequences~~ Synthetic construct ~~sequences~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4E2J FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e2j]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E2J FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MOF:MOMETASONE+FUROATE'>MOF</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MOF:MOMETASONE+FUROATE'>MOF</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=4e2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e2j OCA], [~~http~~://pdbe.org/4e2j PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4e2j RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4e2j PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4e2j 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=4e2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e2j OCA], [https://pdbe.org/4e2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e2j RCSB], [https://www.ebi.ac.uk/pdbsum/4e2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e2j ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.		[[https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>		[[https://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:

	==See Also==		==See Also==
	*[[Glucocorticoid receptor\|Glucocorticoid receptor]]		*[[Glucocorticoid receptor 3D structures\|Glucocorticoid receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Synthetic construct ~~sequences~~]]		[[Category: Synthetic construct]]
	[[Category: Deshpande, K]]		[[Category: Deshpande K]]
	[[Category: Kohn~~, J A~~]]		[[Category: Kohn JA]]
	[[Category: Ortlund~~, E A]]~~		[[Category: Ortlund EA]]
	~~[[Category: Glucocorticoid receptor]]~~
	~~[[Category: Hormone-hormone activator complex]]~~
	~~[[Category: Nuclear receptor ligand binding domain]]~~
	~~[[Category: Steroid binding protein~~]]

OCA at 07:32, 27 March 2019

2019-03-27T07:32:07Z

← Older revision		Revision as of 07:32, 27 March 2019
Line 1:		Line 1:

	==X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment==		==X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment==
	<StructureSection load='4e2j' size='340' side='right' caption='[[4e2j]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4e2j' size='340' side='right'caption='[[4e2j]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e2j]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E2J FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e2j]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E2J FirstGlance]. <br>
Line 27:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Large Structures]]
	[[Category: Synthetic construct sequences]]		[[Category: Synthetic construct sequences]]
	[[Category: Deshpande, K]]		[[Category: Deshpande, K]]

OCA at 07:21, 11 August 2016

2016-08-11T07:21:48Z

← Older revision		Revision as of 07:21, 11 August 2016
Line 1:		Line 1:

	==X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment==		==X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment==
	<StructureSection load='4e2j' size='340' side='right' caption='[[4e2j]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4e2j' size='340' side='right' caption='[[4e2j]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e2j]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Synthetic_construct~~ Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E2J FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e2j]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E2J FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MOF:MOMETASONE+FUROATE'>MOF</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MOF:MOMETASONE+FUROATE'>MOF</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=4e2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e2j OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e2j RCSB], [http://www.ebi.ac.uk/pdbsum/4e2j 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=4e2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e2j OCA], [http://pdbe.org/4e2j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e2j RCSB], [http://www.ebi.ac.uk/pdbsum/4e2j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e2j ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 18:		Line 19:
	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 4e2j" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Synthetic construct]]		[[Category: Synthetic construct sequences]]
	[[Category: Deshpande, K]]		[[Category: Deshpande, K]]
	[[Category: Kohn, J A]]		[[Category: Kohn, J A]]

OCA at 07:51, 20 January 2015

2015-01-20T07:51:22Z

← Older revision		Revision as of 07:51, 20 January 2015
Line 1:		Line 1:
	~~{{STRUCTURE_4e2j\| PDB=4e2j \| SCENE= }}~~		==X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment==
	===X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment===		<StructureSection load='4e2j' size='340' side='right' caption='[[4e2j]], [[Resolution\|resolution]] 2.50Å' scene=''>
	~~{{ABSTRACT_PUBMED_22437833}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4e2j]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E2J FirstGlance]. <br>
	==Disease==		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MOF:MOMETASONE+FUROATE'>MOF</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=4e2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e2j OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e2j RCSB], [http://www.ebi.ac.uk/pdbsum/4e2j PDBsum]</span></td></tr>
			</table>
			== Disease ==
	[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.		[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
			== Function ==
			[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Steroid receptors (SRs) are the largest family of metazoan transcription factors and control genes involved in development, endocrine signaling, reproduction, immunity, and cancer. The entire hormone receptor system is driven by a molecular switch triggered by the binding of small lipophilic ligands. This makes the SRs ideal pharmaceutical targets, yet even the best clinically approved synthetic steroidal agonists are prone to cross-reactivity and off-target pharmacology. The mechanism underlying this promiscuity is derived from the fact that SRs share common structural features derived from their evolutionary relationship. More often than not, rational attempts to probe SR drug selectivity via mutagenesis fail even when high quality structural and functional data are available due to the fact that important mutations often result in nonfunctional receptors. This highlights the fact that SRs suffer from instability, preventing in-depth mutational analysis and hampering crystallization of key receptor-ligand complexes. We have taken a unique approach to address this problem by using a resurrected ancestral protein to determine the structure of a previously intractable complex and identified the structural mechanisms that confer activation and selectivity for a widely used glucocorticoid, mometasone furoate. Moreover, we have identified a single residue located outside of the ligand-binding pocket that controls mometasone furoate antagonism versus agonism in the human mineralocorticoid receptor.

	~~==Function==~~		Deciphering Modern Glucocorticoid Cross-pharmacology Using Ancestral Corticosteroid Receptors.,Kohn JA, Deshpande K, Ortlund EA J Biol Chem. 2012 May 11;287(20):16267-75. Epub 2012 Mar 21. PMID:22437833<ref>PMID:22437833</ref>
	~~[[http://www~~.~~uniprot~~.~~org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain~~ (~~AF-2~~) ~~but not of the modulating N-terminal domain (AF~~-1). ~~Required with NCOA1 to control energy balance between white and brown adipose tissues~~.<ref>PMID:~~9430642~~</ref>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[4e2j]] is~~ a ~~4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Synthetic_construct Synthetic construct]~~. ~~Full crystallographic information is available from [http:/~~/~~oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA].~~		</div>

	==See Also==		==See Also==
	*[[Glucocorticoid receptor\|Glucocorticoid receptor]]		*[[Glucocorticoid receptor\|Glucocorticoid receptor]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:022437833</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Synthetic construct]]		[[Category: Synthetic construct]]
	[[Category: Deshpande, K.]]		[[Category: Deshpande, K]]
	[[Category: Kohn, J A.]]		[[Category: Kohn, J A]]
	[[Category: Ortlund, E A.]]		[[Category: Ortlund, E A]]
	[[Category: Glucocorticoid receptor]]		[[Category: Glucocorticoid receptor]]
	[[Category: Hormone-hormone activator complex]]		[[Category: Hormone-hormone activator complex]]
	[[Category: Nuclear receptor ligand binding domain]]		[[Category: Nuclear receptor ligand binding domain]]
	[[Category: Steroid binding protein]]		[[Category: Steroid binding protein]]

OCA at 09:11, 24 March 2013

2013-03-24T09:11:26Z

← Older revision		Revision as of 09:11, 24 March 2013
Line 1:		Line 1:
	~~[[Image:4e2j.png\|left\|200px]]~~

	{{STRUCTURE_4e2j\| PDB=4e2j \| SCENE= }}		{{STRUCTURE_4e2j\| PDB=4e2j \| SCENE= }}
			===X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment===
			{{ABSTRACT_PUBMED_22437833}}

	===X-~~Ray Crystal Structure~~ of the ~~Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate~~ and ~~TIF~~-~~2 coactivator fragment===~~		==Disease==
			[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.

	~~{{ABSTRACT_PUBMED_22437833}}~~		==Function==
			[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
	<ref group="xtra">PMID:022437833</ref><references group="xtra"/>		<ref group="xtra">PMID:022437833</ref><references group="xtra"/><references/>
	[[Category: Synthetic construct]]		[[Category: Synthetic construct]]
	[[Category: Deshpande, K.]]		[[Category: Deshpande, K.]]

OCA at 05:17, 20 October 2012

2012-10-20T05:17:46Z

← Older revision		Revision as of 05:17, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[4e2j]] is a 4 chain structure ~~of [[Glucocorticoid receptor]]~~ with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA].		[[4e2j]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA].

	==See Also==		==See Also==

OCA at 09:35, 25 July 2012

2012-07-25T09:35:40Z

← Older revision		Revision as of 09:35, 25 July 2012
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	[[Image:4e2j.png\|left\|200px]]		[[Image:4e2j.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_4e2j", 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_4e2j\| PDB=4e2j \| SCENE= }}		{{STRUCTURE_4e2j\| PDB=4e2j \| SCENE= }}

	===X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment===		===X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_22437833}}, adds the Publication Abstract to the page~~
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	~~-->~~
	{{ABSTRACT_PUBMED_22437833}}		{{ABSTRACT_PUBMED_22437833}}

OCA at 05:08, 30 May 2012

2012-05-30T05:08:51Z

← Older revision		Revision as of 05:08, 30 May 2012
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	[[Image:4e2j.~~jpg~~\|left\|200px]]		[[Image:4e2j.png\|left\|200px]]

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	===X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment===		===X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment===


			<!--
			The line below this paragraph, {{ABSTRACT_PUBMED_22437833}}, adds the Publication Abstract to the page
			(as it appears on PubMed at http://www.pubmed.gov), where 22437833 is the PubMed ID number.
			-->
			{{ABSTRACT_PUBMED_22437833}}

	==About this Structure==		==About this Structure==
	[[4e2j]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA].		[[4e2j]] is a 4 chain structure of [[Glucocorticoid receptor]] with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E2J OCA].

			==See Also==
			*[[Glucocorticoid receptor\|Glucocorticoid receptor]]

			==Reference==
			<ref group="xtra">PMID:022437833</ref><references group="xtra"/>
	[[Category: Synthetic construct]]		[[Category: Synthetic construct]]
	[[Category: Deshpande, K.]]		[[Category: Deshpande, K.]]

OCA at 07:54, 28 March 2012

2012-03-28T07:54:49Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:4e2j.jpg|left|200px]]
-The entry 4e2j is ON HOLD  until Paper Publication
+<!--
-Authors: Kohn, J.A., Deshpande, K., Ortlund, E.A.
+===X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment===
-Description: X-Ray Crystal Structure of the Ancestral Glucocorticoid Receptor 2 ligand binding domain in complex with mometasone furoate and TIF-2 coactivator fragment