3fxv: Difference between revisions

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{{Seed}}
[[Image:3fxv.jpg|left|200px]]


<!--
==Identification of an N-oxide pyridine GW4064 analogue as a potent FXR agonist==
The line below this paragraph, containing "STRUCTURE_3fxv", creates the "Structure Box" on the page.
<StructureSection load='3fxv' size='340' side='right'caption='[[3fxv]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[3fxv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FXV FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.26&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=643:6-(4-{[3-(3,5-DICHLOROPYRIDIN-4-YL)-5-(1-METHYLETHYL)ISOXAZOL-4-YL]METHOXY}-2-METHYLPHENYL)-1-METHYL-1H-INDOLE-3-CARBOXYLIC+ACID'>643</scene></td></tr>
{{STRUCTURE_3fxv| PDB=3fxv |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3fxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fxv OCA], [https://pdbe.org/3fxv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fxv RCSB], [https://www.ebi.ac.uk/pdbsum/3fxv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fxv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NR1H4_HUMAN NR1H4_HUMAN] Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.<ref>PMID:10334992</ref> <ref>PMID:10334993</ref> <ref>PMID:12815072</ref> <ref>PMID:15471871</ref> <ref>PMID:12718892</ref> <ref>PMID:18621523</ref> <ref>PMID:19410460</ref> <ref>PMID:19586769</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fx/3fxv_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3fxv ConSurf].
<div style="clear:both"></div>


===Identification of an N-oxide pyridine GW4064 analogue as a potent FXR agonist===
==See Also==
 
*[[Bile acid receptor 3D structures|Bile acid receptor 3D structures]]
 
== References ==
<!--
<references/>
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(as it appears on PubMed at http://www.pubmed.gov), where 19328688 is the PubMed ID number.
</StructureSection>
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{{ABSTRACT_PUBMED_19328688}}
 
==About this Structure==
3FXV is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FXV OCA].
 
==Reference==
<ref group="xtra">PMID:19328688</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Benson, G M.]]
[[Category: Large Structures]]
[[Category: Bleicher, K.]]
[[Category: Benson GM]]
[[Category: Chen, L.]]
[[Category: Bleicher K]]
[[Category: Feng, S.]]
[[Category: Chen L]]
[[Category: Grether, U.]]
[[Category: Feng S]]
[[Category: He, Y.]]
[[Category: Grether U]]
[[Category: Hong, G.]]
[[Category: He Y]]
[[Category: Kuhn, B.]]
[[Category: Hong D]]
[[Category: Martin, R.]]
[[Category: Kuhn B]]
[[Category: Plancher, J M.]]
[[Category: Martin R]]
[[Category: Richter, H.]]
[[Category: Plancher J-M]]
[[Category: Rudolph, M G.]]
[[Category: Richter H]]
[[Category: Wang, S.]]
[[Category: Rudolph MG]]
[[Category: Yang, M.]]
[[Category: Wang Z]]
[[Category: Zhang, Z.]]
[[Category: Yang M]]
[[Category: Activator]]
[[Category: Zhang Z]]
[[Category: Acyltransferase]]
[[Category: Alternative splicing]]
[[Category: Bile acid]]
[[Category: Cholesterol]]
[[Category: Chromosomal rearrangement]]
[[Category: Dna-binding]]
[[Category: Hormone receptor]]
[[Category: Metal-binding]]
[[Category: Nuclear receptor]]
[[Category: Nucleus]]
[[Category: Phosphoprotein]]
[[Category: Polymorphism]]
[[Category: Proto-oncogene]]
[[Category: Receptor]]
[[Category: Transcription]]
[[Category: Transcription regulation]]
[[Category: Transferase]]
[[Category: Ubl conjugation]]
[[Category: Zinc]]
[[Category: Zinc-finger]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 15 10:25:17 2009''

Latest revision as of 09:37, 3 April 2024

Identification of an N-oxide pyridine GW4064 analogue as a potent FXR agonistIdentification of an N-oxide pyridine GW4064 analogue as a potent FXR agonist

Structural highlights

3fxv is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.26Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NR1H4_HUMAN Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.[1] [2] [3] [4] [5] [6] [7] [8]

Evolutionary Conservation

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

See Also

References

  1. ↑ Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, Shan B. Identification of a nuclear receptor for bile acids. Science. 1999 May 21;284(5418):1362-5. PMID:10334992
  2. ↑ Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD, Lehmann JM. Bile acids: natural ligands for an orphan nuclear receptor. Science. 1999 May 21;284(5418):1365-8. PMID:10334993
  3. ↑ Holt JA, Luo G, Billin AN, Bisi J, McNeill YY, Kozarsky KF, Donahee M, Wang DY, Mansfield TA, Kliewer SA, Goodwin B, Jones SA. Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev. 2003 Jul 1;17(13):1581-91. Epub 2003 Jun 18. PMID:12815072 doi:10.1101/gad.1083503
  4. ↑ Ananthanarayanan M, Li S, Balasubramaniyan N, Suchy FJ, Walsh MJ. Ligand-dependent activation of the farnesoid X-receptor directs arginine methylation of histone H3 by CARM1. J Biol Chem. 2004 Dec 24;279(52):54348-57. Epub 2004 Oct 6. PMID:15471871 doi:M410021200
  5. ↑ Downes M, Verdecia MA, Roecker AJ, Hughes R, Hogenesch JB, Kast-Woelbern HR, Bowman ME, Ferrer JL, Anisfeld AM, Edwards PA, Rosenfeld JM, Alvarez JG, Noel JP, Nicolaou KC, Evans RM. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol Cell. 2003 Apr;11(4):1079-92. PMID:12718892
  6. ↑ Akwabi-Ameyaw A, Bass JY, Caldwell RD, Caravella JA, Chen L, Creech KL, Deaton DN, Jones SA, Kaldor I, Liu Y, Madauss KP, Marr HB, McFadyen RB, Miller AB, Iii FN, Parks DJ, Spearing PK, Todd D, Williams SP, Wisely GB. Conformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064. Bioorg Med Chem Lett. 2008 Aug 1;18(15):4339-43. Epub 2008 Jun 28. PMID:18621523 doi:10.1016/j.bmcl.2008.06.073
  7. ↑ Bass JY, Caldwell RD, Caravella JA, Chen L, Creech KL, Deaton DN, Madauss KP, Marr HB, McFadyen RB, Miller AB, Parks DJ, Todd D, Williams SP, Wisely GB. Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064. Bioorg Med Chem Lett. 2009 Jun 1;19(11):2969-73. Epub 2009 Apr 18. PMID:19410460 doi:10.1016/j.bmcl.2009.04.047
  8. ↑ Akwabi-Ameyaw A, Bass JY, Caldwell RD, Caravella JA, Chen L, Creech KL, Deaton DN, Madauss KP, Marr HB, McFadyen RB, Miller AB, Navas F 3rd, Parks DJ, Spearing PK, Todd D, Williams SP, Bruce Wisely G. FXR agonist activity of conformationally constrained analogs of GW 4064. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4733-9. Epub 2009 Jun 21. PMID:19586769 doi:10.1016/j.bmcl.2009.06.062

3fxv, resolution 2.26Å

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