3o1d: Difference between revisions

Revision as of 10:38, 14 December 2022

Structure-function study of Gemini derivatives with two different side chains at C-20, Gemini-0072 and Gemini-0097.

Structural highlights

3o1d is a 2 chain structure with sequence from Danio rerio and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	G72
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

Derivatives of vitamin D(3) containing a second side-chain emanating at C-20 are known as gemini and act as vitamin D receptor agonists. Recently, two of these, namely Gemini-0072 and the epimeric Gemini-0097, were selected for further studies in view of their high biological activities and lack of hypercalcemic effects. We now show that the two analogs recruit coactivator SRC-1 better than the parental gemini and act as VDR superagonists. The crystal structures of complexes of zVDR with Gemini-0072 and Gemini-0097 indicate that these ligands induce an extra cavity within the ligand-binding pocket similar to gemini and that their superagonistic activity is due to an increased stabilization of helix H12.

Structure-function study of gemini derivatives with two different side chains at C-20, Gemini-0072 and Gemini-0097.,Huet T, Maehr H, Lee HJ, Uskokovic MR, Suh N, Moras D, Rochel N Medchemcomm. 2011;2(5):424-429. PMID:22180837^[2]

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:https://dx.doi.org/10.1016/j.jsbmb.2006.12.003
↑ Huet T, Maehr H, Lee HJ, Uskokovic MR, Suh N, Moras D, Rochel N. Structure-function study of gemini derivatives with two different side chains at C-20, Gemini-0072 and Gemini-0097. Medchemcomm. 2011;2(5):424-429. PMID:22180837 doi:10.1039/C1MD00059D

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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:https://dx.doi.org/10.1016/j.jsbmb.2006.12.003

[2] Huet T, Maehr H, Lee HJ, Uskokovic MR, Suh N, Moras D, Rochel N. Structure-function study of gemini derivatives with two different side chains at C-20, Gemini-0072 and Gemini-0097. Medchemcomm. 2011;2(5):424-429. PMID:22180837 doi:10.1039/C1MD00059D

[1]

[2]

@@ Line 3: / Line 3: @@
 <StructureSection load='3o1d' size='340' side='right'caption='[[3o1d]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3o1d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O1D FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3o1d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O1D FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G72:(1R,3R,7E,17BETA)-17-[(1S)-6,6,6-TRIFLUORO-5-HYDROXY-1-(4-HYDROXY-4-METHYLPENTYL)-5-(TRIFLUOROMETHYL)HEX-3-YN-1-YL]-9,10-SECOESTRA-5,7-DIENE-1,3-DIOL'>G72</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2hc4|2hc4]], [[2hcd|2hcd]], [[3o1e|3o1e]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">vdra, nr1i1a, vdr ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3o1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o1d OCA], [https://pdbe.org/3o1d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o1d RCSB], [https://www.ebi.ac.uk/pdbsum/3o1d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o1d ProSAT]</span></td></tr>
 </table>
-== 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.
 == Function ==
-[[https://www.uniprot.org/uniprot/VDRA_DANRE 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.<ref>PMID:17218092</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>
+[https://www.uniprot.org/uniprot/VDRA_DANRE 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.<ref>PMID:17218092</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Brachidanio rerio]]
+[[Category: Danio rerio]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Huet, T]]
+[[Category: Huet T]]
-[[Category: Moras, D]]
+[[Category: Moras D]]
-[[Category: Rochel, N]]
+[[Category: Rochel N]]
-[[Category: Nucleus]]
-[[Category: Transcription factor]]
-[[Category: Transcription-transcription activator complex]]
-[[Category: Vitamin d]]

3o1d: Difference between revisions

Revision as of 10:38, 14 December 2022

Structure-function study of Gemini derivatives with two different side chains at C-20, Gemini-0072 and Gemini-0097.

Structural highlights

Function

Publication Abstract from PubMed

References

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