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5xzf

From Proteopedia

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Vitamin D receptor with a synthetic ligand ADRO1

Structural highlights

5xzf is a 2 chain structure with sequence from Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MED1_HUMAN Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11]

Publication Abstract from PubMed

Both 25 R- and 25 S-25-adamantyl-23-yne-26,27-dinor-1alpha,25-dihydroxyvitamin D3 (4a and 4b) were stereoselectively synthesized by a Pd(0)-catalyzed ring closure and Suzuki-Miyaura coupling between enol-triflate 7 and alkenyl-boronic ester 8. The 25 S isomer (4b) showed high vitamin D receptor (VDR) affinity (50% of that of the natural hormone 1alpha,25-dihydroxyvitamin D3, 1) and transactivation potency (kidney HEK293, 90%). In endogenous gene expression, it showed high cell-type selectivity for kidney cells (HEK293, CYP24A1 160% of 1), bone cells (MG63, osteocalcin 64%), and monocytes (U937, CAMP 96%) over intestine (SW480, CYP24A1 8%) and skin (HaCaT, CYP24A1 7%) cells. The X-ray crystal structural analysis of 4b in complex with rat VDR-ligand binding domain (LBD) showed the highest Calpha positional shift from the 1/VDR-LBD complex at helix 11. Helix 11 of the 4b and 1 VDR-LBD complexes also showed significant differences in surface properties. These results suggest that 4b should be examined further as another candidate for a mild preventive osteoporosis agent.

25 S-Adamantyl-23-yne-26,27-dinor-1alpha,25-dihydroxyvitamin D3: Synthesis, Tissue Selective Biological Activities, and X-ray Crystal Structural Analysis of Its Vitamin D Receptor Complex.,Otero R, Ishizawa M, Numoto N, Ikura T, Ito N, Tokiwa H, Mourino A, Makishima M, Yamada S J Med Chem. 2018 Jul 23. doi: 10.1021/acs.jmedchem.8b00427. PMID:29989817^[12]

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

References

↑ Yuan CX, Ito M, Fondell JD, Fu ZY, Roeder RG. The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7939-44. PMID:9653119
↑ Zhang J, Fondell JD. Identification of mouse TRAP100: a transcriptional coregulatory factor for thyroid hormone and vitamin D receptors. Mol Endocrinol. 1999 Jul;13(7):1130-40. PMID:10406464
↑ Wang Q, Sharma D, Ren Y, Fondell JD. A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression. J Biol Chem. 2002 Nov 8;277(45):42852-8. Epub 2002 Sep 5. PMID:12218053 doi:10.1074/jbc.M206061200
↑ Ge K, Guermah M, Yuan CX, Ito M, Wallberg AE, Spiegelman BM, Roeder RG. Transcription coactivator TRAP220 is required for PPAR gamma 2-stimulated adipogenesis. Nature. 2002 May 30;417(6888):563-7. PMID:12037571 doi:10.1038/417563a
↑ Kang YK, Guermah M, Yuan CX, Roeder RG. The TRAP/Mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2642-7. Epub 2002 Feb 26. PMID:11867769 doi:10.1073/pnas.261715899
↑ Coulthard VH, Matsuda S, Heery DM. An extended LXXLL motif sequence determines the nuclear receptor binding specificity of TRAP220. J Biol Chem. 2003 Mar 28;278(13):10942-51. Epub 2003 Jan 29. PMID:12556447 doi:10.1074/jbc.M212950200
↑ Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG. Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Mol Cell. 2003 Nov;12(5):1137-49. PMID:14636573
↑ Wu Q, Burghardt R, Safe S. Vitamin D-interacting protein 205 (DRIP205) coactivation of estrogen receptor alpha (ERalpha) involves multiple domains of both proteins. J Biol Chem. 2004 Dec 17;279(51):53602-12. Epub 2004 Oct 5. PMID:15471764 doi:10.1074/jbc.M409778200
↑ Malik S, Guermah M, Yuan CX, Wu W, Yamamura S, Roeder RG. Structural and functional organization of TRAP220, the TRAP/mediator subunit that is targeted by nuclear receptors. Mol Cell Biol. 2004 Sep;24(18):8244-54. PMID:15340084 doi:10.1128/MCB.24.18.8244-8254.2004
↑ Zhang X, Krutchinsky A, Fukuda A, Chen W, Yamamura S, Chait BT, Roeder RG. MED1/TRAP220 exists predominantly in a TRAP/ Mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription. Mol Cell. 2005 Jul 1;19(1):89-100. PMID:15989967 doi:10.1016/j.molcel.2005.05.015
↑ Udayakumar TS, Belakavadi M, Choi KH, Pandey PK, Fondell JD. Regulation of Aurora-A kinase gene expression via GABP recruitment of TRAP220/MED1. J Biol Chem. 2006 May 26;281(21):14691-9. Epub 2006 Mar 30. PMID:16574658 doi:M600163200
↑ Otero R, Ishizawa M, Numoto N, Ikura T, Ito N, Tokiwa H, Mourino A, Makishima M, Yamada S. 25 S-Adamantyl-23-yne-26,27-dinor-1alpha,25-dihydroxyvitamin D3: Synthesis, Tissue Selective Biological Activities, and X-ray Crystal Structural Analysis of Its Vitamin D Receptor Complex. J Med Chem. 2018 Jul 23. doi: 10.1021/acs.jmedchem.8b00427. PMID:29989817 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b00427

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5xzf"

@@ Line 1: / Line 1: @@
 ==Vitamin D receptor with a synthetic ligand ADRO1==
-<StructureSection load='5xzf' size='340' side='right' caption='[[5xzf]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='5xzf' size='340' side='right'caption='[[5xzf]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xzf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XZF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xzf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XZF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XZF FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8J0:(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,6S)-6-(1-adamantyl)-6-oxidanyl-hex-4-yn-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol'>8J0</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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]] 2.1&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Vdr, Nr1i1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8J0:(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R,6S)-6-(1-adamantyl)-6-oxidanyl-hex-4-yn-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol'>8J0</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=5xzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xzf OCA], [http://pdbe.org/5xzf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xzf RCSB], [http://www.ebi.ac.uk/pdbsum/5xzf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xzf 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=5xzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xzf OCA], [https://pdbe.org/5xzf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xzf RCSB], [https://www.ebi.ac.uk/pdbsum/5xzf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xzf ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/VDR_RAT VDR_RAT]] 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. Recruited to promoters via its interaction with the WINAC complex subunit BAZ1B/WSTF, which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.<ref>PMID:17227670</ref>  [[http://www.uniprot.org/uniprot/MED1_HUMAN MED1_HUMAN]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.<ref>PMID:9653119</ref> <ref>PMID:10406464</ref> <ref>PMID:12218053</ref> <ref>PMID:12037571</ref> <ref>PMID:11867769</ref> <ref>PMID:12556447</ref> <ref>PMID:14636573</ref> <ref>PMID:15471764</ref> <ref>PMID:15340084</ref> <ref>PMID:15989967</ref> <ref>PMID:16574658</ref>
+[https://www.uniprot.org/uniprot/MED1_HUMAN MED1_HUMAN] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.<ref>PMID:9653119</ref> <ref>PMID:10406464</ref> <ref>PMID:12218053</ref> <ref>PMID:12037571</ref> <ref>PMID:11867769</ref> <ref>PMID:12556447</ref> <ref>PMID:14636573</ref> <ref>PMID:15471764</ref> <ref>PMID:15340084</ref> <ref>PMID:15989967</ref> <ref>PMID:16574658</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 5xzf" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Vitamin D receptor 3D structures|Vitamin D receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Buffalo rat]]
+[[Category: Homo sapiens]]
-[[Category: Ikura, T]]
+[[Category: Large Structures]]
-[[Category: Ito, N]]
+[[Category: Rattus norvegicus]]
-[[Category: Makishima, M]]
+[[Category: Ikura T]]
-[[Category: Mourino, A]]
+[[Category: Ito N]]
-[[Category: Numoto, N]]
+[[Category: Makishima M]]
-[[Category: Otero, R]]
+[[Category: Mourino A]]
-[[Category: Yamada, S]]
+[[Category: Numoto N]]
-[[Category: Adamantan]]
+[[Category: Otero R]]
-[[Category: Transcription]]
+[[Category: Yamada S]]
-[[Category: Vitamin d analogue]]
-[[Category: Vitamin d receptor]]

5xzf

From Proteopedia

Current revision

Vitamin D receptor with a synthetic ligand ADRO1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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