3fc6: Difference between revisions

Revision as of 08:00, 5 December 2018

hRXRalpha & mLXRalpha with an indole Pharmacophore, SB786875

Structural highlights

3fc6 is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	LX2, REA
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[RXRA_HUMAN] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.^[1] ^[2] ^[3] ^[4]

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

A novel series of 1H-indol-1-yl tertiary amine LXR agonists has been designed. Compounds from this series were potent agonists with good rat pharmacokinetic parameters. In addition, the crystal structure of an LXR agonist bound to LXRalpha will be disclosed.

Synthesis and SAR of potent LXR agonists containing an indole pharmacophore.,Washburn DG, Hoang TH, Campobasso N, Smallwood A, Parks DJ, Webb CL, Frank KA, Nord M, Duraiswami C, Evans C, Jaye M, Thompson SK Bioorg Med Chem Lett. 2009 Jan 9. PMID:19167885^[5]

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

References

↑ Gorla-Bajszczak A, Juge-Aubry C, Pernin A, Burger AG, Meier CA. Conserved amino acids in the ligand-binding and tau(i) domains of the peroxisome proliferator-activated receptor alpha are necessary for heterodimerization with RXR. Mol Cell Endocrinol. 1999 Jan 25;147(1-2):37-47. PMID:10195690
↑ Harish S, Ashok MS, Khanam T, Rangarajan PN. Serine 27, a human retinoid X receptor alpha residue, phosphorylated by protein kinase A is essential for cyclicAMP-mediated downregulation of RXRalpha function. Biochem Biophys Res Commun. 2000 Dec 29;279(3):853-7. PMID:11162439 doi:10.1006/bbrc.2000.4043
↑ Tsutsumi T, Suzuki T, Shimoike T, Suzuki R, Moriya K, Shintani Y, Fujie H, Matsuura Y, Koike K, Miyamura T. Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity. Hepatology. 2002 Apr;35(4):937-46. PMID:11915042 doi:10.1053/jhep.2002.32470
↑ Santos NC, Kim KH. Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to follicle-stimulating hormone signaling. Endocrinology. 2010 May;151(5):2361-72. doi: 10.1210/en.2009-1338. Epub 2010 Mar , 9. PMID:20215566 doi:10.1210/en.2009-1338
↑ Washburn DG, Hoang TH, Campobasso N, Smallwood A, Parks DJ, Webb CL, Frank KA, Nord M, Duraiswami C, Evans C, Jaye M, Thompson SK. Synthesis and SAR of potent LXR agonists containing an indole pharmacophore. Bioorg Med Chem Lett. 2009 Jan 9. PMID:19167885 doi:S0960-894X(09)00009-2

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Gorla-Bajszczak A, Juge-Aubry C, Pernin A, Burger AG, Meier CA. Conserved amino acids in the ligand-binding and tau(i) domains of the peroxisome proliferator-activated receptor alpha are necessary for heterodimerization with RXR. Mol Cell Endocrinol. 1999 Jan 25;147(1-2):37-47. PMID:10195690

[2] Harish S, Ashok MS, Khanam T, Rangarajan PN. Serine 27, a human retinoid X receptor alpha residue, phosphorylated by protein kinase A is essential for cyclicAMP-mediated downregulation of RXRalpha function. Biochem Biophys Res Commun. 2000 Dec 29;279(3):853-7. PMID:11162439 doi:10.1006/bbrc.2000.4043

[3] Tsutsumi T, Suzuki T, Shimoike T, Suzuki R, Moriya K, Shintani Y, Fujie H, Matsuura Y, Koike K, Miyamura T. Interaction of hepatitis C virus core protein with retinoid X receptor alpha modulates its transcriptional activity. Hepatology. 2002 Apr;35(4):937-46. PMID:11915042 doi:10.1053/jhep.2002.32470

[4] Santos NC, Kim KH. Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to follicle-stimulating hormone signaling. Endocrinology. 2010 May;151(5):2361-72. doi: 10.1210/en.2009-1338. Epub 2010 Mar , 9. PMID:20215566 doi:10.1210/en.2009-1338

[5] Washburn DG, Hoang TH, Campobasso N, Smallwood A, Parks DJ, Webb CL, Frank KA, Nord M, Duraiswami C, Evans C, Jaye M, Thompson SK. Synthesis and SAR of potent LXR agonists containing an indole pharmacophore. Bioorg Med Chem Lett. 2009 Jan 9. PMID:19167885 doi:S0960-894X(09)00009-2

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[2]

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[5]

@@ Line 1: / Line 1: @@
 ==hRXRalpha & mLXRalpha with an indole Pharmacophore, SB786875==
 <StructureSection load='3fc6' size='340' side='right' caption='[[3fc6]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[3fc6]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FC6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FC6 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LX2:[4-(3-{[2-CHLORO-3-(TRIFLUOROMETHYL)BENZYL](2,2-DIPHENYLETHYL)AMINO}PROPOXY)-1H-INDOL-1-YL]ACETIC+ACID'>LX2</scene>, <scene name='pdbligand=REA:RETINOIC+ACID'>REA</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=3fc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fc6 OCA], [http://pdbe.org/3fc6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fc6 RCSB], [http://www.ebi.ac.uk/pdbsum/3fc6 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=3fc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fc6 OCA], [http://pdbe.org/3fc6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fc6 RCSB], [http://www.ebi.ac.uk/pdbsum/3fc6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fc6 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 12: / Line 13: @@
 Check<jmol>
    <jmolCheckbox>
-     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fc/3fc6_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fc/3fc6_consurf.spt"</scriptWhenChecked>
      <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 56: / Line 57: @@
 [[Category: Nuclear hormone receptor]]
 [[Category: Nucleus]]
+[[Category: Polymorphism]]
 [[Category: Receptor]]
 [[Category: Transcription]]
 [[Category: Transcription regulation]]
+[[Category: Ubl conjugation]]
+[[Category: Zinc]]
 [[Category: Zinc-finger]]

3fc6: Difference between revisions

Revision as of 08:00, 5 December 2018

hRXRalpha & mLXRalpha with an indole Pharmacophore, SB786875

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

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Proteopedia Page Contributors and Editors (what is this?)

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