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4ia7

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Revision as of 09:44, 4 August 2016

Diastereotopic and Deuterium Effects in Gemini

Structural highlights

4ia7 is a 2 chain structure with sequence from Brachidanio rerio. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3o1d, 3o1e, 2hcd, 4ia1, 4ia2, 4ia3
Gene:	vdra, nr1i1a, vdr (Brachidanio rerio)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[VDRA_DANRE] Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Regulates transcription of hormone sensitive genes via its association with the WINAC complex, a chromatin-remodeling complex. Plays a central role in calcium homeostasis.^[1] [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.^[2]

Publication Abstract from PubMed

Changing the geminal methyl groups on 1alpha,25 dihydroxyvitamin D3 and its analogs to the deuterio versions generally improves the bioactivity. Derivatives of 1alpha,25 dihydroxyvitamin D3 with two chains emanating at C20, commonly referred to as gemini, are subject to the same phenomenon. Additionally, gemini with different side chains are susceptible to bioactivity differentials where the C17-20 threo configuration usually imparts higher activity than the corresponding erythro arrangement. In an effort to analyze the deuterium effect on gemini with minimal diastereotopic distortion, we synthesized gemini with equal side chains but introduced deuterium diastereospecifically on either chain. We solved the crystal structures of these compounds in the zebra fish zVDR ligand binding domain as complexes with NCoA-2 coactivator peptide and correlated the findings with growth inhibition in a breast cancer cell line.

Diastereotopic and Deuterium Effects in Gemini.,Maehr H, Rochel N, Lee HJ, Suh N, Milan UR J Med Chem. 2013 Apr 8. PMID:23566225^[3]

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

References

↑ Ciesielski F, Rochel N, Moras D. Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: remodelling the LBP with one side chain rotation. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):235-42. Epub 2007 Jan 10. PMID:17218092 doi:http://dx.doi.org/10.1016/j.jsbmb.2006.12.003
↑ Voegel JJ, Heine MJ, Tini M, Vivat V, Chambon P, Gronemeyer H. The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways. EMBO J. 1998 Jan 15;17(2):507-19. PMID:9430642 doi:10.1093/emboj/17.2.507
↑ Maehr H, Rochel N, Lee HJ, Suh N, Milan UR. Diastereotopic and Deuterium Effects in Gemini. J Med Chem. 2013 Apr 8. PMID:23566225 doi:10.1021/jm400032t

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ia7"

@@ Line 1: / Line 1: @@
 ==Diastereotopic and Deuterium Effects in Gemini==
 <StructureSection load='4ia7' size='340' side='right' caption='[[4ia7]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ia7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IA7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IA7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4ia7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IA7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IA7 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BIV:21-NOR-9,10-SECOCHOLESTA-5,7,10(19)-TRIENE-1,3,25-TRIOL,+20-(4-HYDROXY-4-METHYLPENTYL)-,+(1A,3B,5Z,7E)'>BIV</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3o1d|3o1d]], [[3o1e|3o1e]], [[2hcd|2hcd]], [[4ia1|4ia1]], [[4ia2|4ia2]], [[4ia3|4ia3]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">vdra, nr1i1a, vdr ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Danio rerio])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">vdra, nr1i1a, vdr ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=4ia7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ia7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ia7 RCSB], [http://www.ebi.ac.uk/pdbsum/4ia7 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=4ia7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ia7 OCA], [http://pdbe.org/4ia7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ia7 RCSB], [http://www.ebi.ac.uk/pdbsum/4ia7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ia7 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 21: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ia7" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Danio rerio]]
+[[Category: Brachidanio rerio]]
 [[Category: Maehr, H]]
 [[Category: Rochel, N]]

4ia7

From Proteopedia

Revision as of 09:44, 4 August 2016

Diastereotopic and Deuterium Effects in Gemini

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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