2q3y: Difference between revisions

Revision as of 16:48, 19 January 2015

Ancestral Corticiod Receptor in Complex with DOC

Structural highlights

2q3y is a 2 chain structure with sequence from Unidentified. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	1CA, GOL
Related:	2q1v, 2q1h
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[SHP_HUMAN] Defects in NR0B2 may be associated with obesity (OBESITY) [MIM:601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.^[1]

Function

[SHP_HUMAN] Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1.^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The structural mechanisms by which proteins have evolved new functions are known only indirectly. We report x-ray crystal structures of a resurrected ancestral protein-the approximately 450 million-year-old precursor of vertebrate glucocorticoid (GR) and mineralocorticoid (MR) receptors. Using structural, phylogenetic, and functional analysis, we identify the specific set of historical mutations that recapitulate the evolution of GR's hormone specificity from an MR-like ancestor. These substitutions repositioned crucial residues to create new receptor-ligand and intraprotein contacts. Strong epistatic interactions occur because one substitution changes the conformational position of another site. "Permissive" mutations-substitutions of no immediate consequence, which stabilize specific elements of the protein and allow it to tolerate subsequent function-switching changes-played a major role in determining GR's evolutionary trajectory.

Crystal structure of an ancient protein: evolution by conformational epistasis.,Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW Science. 2007 Sep 14;317(5844):1544-8. Epub 2007 Aug 16. PMID:17702911^[3]

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

References

↑ Nishigori H, Tomura H, Tonooka N, Kanamori M, Yamada S, Sho K, Inoue I, Kikuchi N, Onigata K, Kojima I, Kohama T, Yamagata K, Yang Q, Matsuzawa Y, Miki T, Seino S, Kim MY, Choi HS, Lee YK, Moore DD, Takeda J. Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):575-80. Epub 2001 Jan 2. PMID:11136233 doi:10.1073/pnas.021544398
↑ Kim JY, Chu K, Kim HJ, Seong HA, Park KC, Sanyal S, Takeda J, Ha H, Shong M, Tsai MJ, Choi HS. Orphan nuclear receptor small heterodimer partner, a novel corepressor for a basic helix-loop-helix transcription factor BETA2/neuroD. Mol Endocrinol. 2004 Apr;18(4):776-90. Epub 2004 Jan 29. PMID:14752053 doi:10.1210/me.2003-0311
↑ Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW. Crystal structure of an ancient protein: evolution by conformational epistasis. Science. 2007 Sep 14;317(5844):1544-8. Epub 2007 Aug 16. PMID:17702911

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Nishigori H, Tomura H, Tonooka N, Kanamori M, Yamada S, Sho K, Inoue I, Kikuchi N, Onigata K, Kojima I, Kohama T, Yamagata K, Yang Q, Matsuzawa Y, Miki T, Seino S, Kim MY, Choi HS, Lee YK, Moore DD, Takeda J. Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):575-80. Epub 2001 Jan 2. PMID:11136233 doi:10.1073/pnas.021544398

[2] Kim JY, Chu K, Kim HJ, Seong HA, Park KC, Sanyal S, Takeda J, Ha H, Shong M, Tsai MJ, Choi HS. Orphan nuclear receptor small heterodimer partner, a novel corepressor for a basic helix-loop-helix transcription factor BETA2/neuroD. Mol Endocrinol. 2004 Apr;18(4):776-90. Epub 2004 Jan 29. PMID:14752053 doi:10.1210/me.2003-0311

[3] Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW. Crystal structure of an ancient protein: evolution by conformational epistasis. Science. 2007 Sep 14;317(5844):1544-8. Epub 2007 Aug 16. PMID:17702911

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2q3y]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q3Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Q3Y FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1CA:DESOXYCORTICOSTERONE'>1CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1CA:DESOXYCORTICOSTERONE'>1CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2q1v|2q1v]], [[2q1h|2q1h]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2q1v|2q1v]], [[2q1h|2q1h]]</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2q3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q3y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2q3y RCSB], [http://www.ebi.ac.uk/pdbsum/2q3y 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=2q3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q3y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2q3y RCSB], [http://www.ebi.ac.uk/pdbsum/2q3y PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/SHP_HUMAN SHP_HUMAN]] Defects in NR0B2 may be associated with obesity (OBESITY) [MIM:[http://omim.org/entry/601665 601665]]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:11136233</ref>
@@ Line 34: / Line 34: @@
 </StructureSection>
 [[Category: Unidentified]]
-[[Category: Bridgham, J T.]]
+[[Category: Bridgham, J T]]
-[[Category: Ortlund, E A.]]
+[[Category: Ortlund, E A]]
-[[Category: Redinbo, M R.]]
+[[Category: Redinbo, M R]]
-[[Category: Thornton, J W.]]
+[[Category: Thornton, J W]]
 [[Category: Cortisol]]
 [[Category: Doc]]

2q3y: Difference between revisions

Revision as of 16:48, 19 January 2015

Ancestral Corticiod Receptor in Complex with DOC

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

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