5azt: Difference between revisions

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<StructureSection load='5azt' size='340' side='right'caption='[[5azt]], [[Resolution|resolution]] 3.45&Aring;' scene=''>
<StructureSection load='5azt' size='340' side='right'caption='[[5azt]], [[Resolution|resolution]] 3.45&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5azt]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AZT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AZT FirstGlance]. <br>
<table><tr><td colspan='2'>[[5azt]] is a 3 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=5AZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AZT FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4M5:(4~{Z},7~{Z},10~{Z},13~{Z},19~{Z})-17-OXIDANYLIDENEDOCOSA-4,7,10,13,19-PENTAENOIC+ACID'>4M5</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4M5:(4~{Z},7~{Z},10~{Z},13~{Z},19~{Z})-17-OXIDANYLIDENEDOCOSA-4,7,10,13,19-PENTAENOIC+ACID'>4M5</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5azv|5azv]]</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=5azt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5azt OCA], [https://pdbe.org/5azt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5azt RCSB], [https://www.ebi.ac.uk/pdbsum/5azt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5azt ProSAT]</span></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPARA, NR1C1, PPAR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5azt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5azt OCA], [http://pdbe.org/5azt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5azt RCSB], [http://www.ebi.ac.uk/pdbsum/5azt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5azt ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/PPARA_HUMAN PPARA_HUMAN]] Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety (By similarity). Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2.<ref>PMID:7684926</ref> <ref>PMID:7629123</ref> <ref>PMID:9556573</ref> <ref>PMID:10195690</ref> [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref> <ref>PMID:7481822</ref> <ref>PMID:9223431</ref> <ref>PMID:9296499</ref> <ref>PMID:9223281</ref> <ref>PMID:10449719</ref> <ref>PMID:12954634</ref> 
[https://www.uniprot.org/uniprot/PPARA_HUMAN PPARA_HUMAN] Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety (By similarity). Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2.<ref>PMID:7684926</ref> <ref>PMID:7629123</ref> <ref>PMID:9556573</ref> <ref>PMID:10195690</ref>  
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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==See Also==
==See Also==
*[[Phenylethanolamine N-methyltransferase 3D structures|Phenylethanolamine N-methyltransferase 3D structures]]
*[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Egawa, D]]
[[Category: Egawa D]]
[[Category: Itoh, T]]
[[Category: Itoh T]]
[[Category: Yamamoto, K]]
[[Category: Yamamoto K]]
[[Category: Activator]]
[[Category: Agonist]]
[[Category: Co-activator]]
[[Category: Covalent]]
[[Category: Dna binding]]
[[Category: Dna binding protein]]
[[Category: Dual agonist]]
[[Category: Ligand binding domain]]
[[Category: Nuclear]]
[[Category: Nuclear receptor]]
[[Category: Nucleus]]
[[Category: Obesity]]
[[Category: Oxidized fatty acid]]
[[Category: Ppre]]
[[Category: Receptor]]
[[Category: Transcription]]
[[Category: Transcription factor]]
[[Category: Transcription regulation]]
[[Category: Zinc-finger]]

Revision as of 09:32, 31 May 2023

Ternary complex of hPPARalpha ligand binding domain, 17-oxoDHA and a SRC1 peptideTernary complex of hPPARalpha ligand binding domain, 17-oxoDHA and a SRC1 peptide

Structural highlights

5azt is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PPARA_HUMAN Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety (By similarity). Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2.[1] [2] [3] [4]

Publication Abstract from PubMed

17-Hydroxy docosahexaenoic acid (17-HDHA) is an oxidized form of docosahexaenoic acid (DHA) and known as a specialized proresolving mediator. We found that a further oxidized product, 17-oxodocosahexaenoic acid (17-oxoDHA), activates peroxisome proliferator-activated receptors gamma (PPARgamma) and PPARalpha in transcriptional assays and thus can be classified as an alpha/gamma dual agonist. ESI mass spectroscopy and X-ray crystallographic analysis showed that 17-oxoDHA binds to PPARgamma and PPARalpha covalently, making 17-oxoDHA the first of a novel class of PPAR agonists, the PPARalpha/gamma dual covalent agonist. Furthermore, the covalent binding sites were identified as Cys285 for PPARgamma and Cys275 for PPARalpha.

17-OxoDHA Is a PPARalpha/gamma Dual Covalent Modifier and Agonist.,Egawa D, Itoh T, Akiyama Y, Saito T, Yamamoto K ACS Chem Biol. 2016 Jul 1. PMID:27337155[5]

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

See Also

References

  1. ↑ Sher T, Yi HF, McBride OW, Gonzalez FJ. cDNA cloning, chromosomal mapping, and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry. 1993 Jun 1;32(21):5598-604. PMID:7684926
  2. ↑ Juge-Aubry CE, Gorla-Bajszczak A, Pernin A, Lemberger T, Wahli W, Burger AG, Meier CA. Peroxisome proliferator-activated receptor mediates cross-talk with thyroid hormone receptor by competition for retinoid X receptor. Possible role of a leucine zipper-like heptad repeat. J Biol Chem. 1995 Jul 28;270(30):18117-22. PMID:7629123
  3. ↑ Yan ZH, Karam WG, Staudinger JL, Medvedev A, Ghanayem BI, Jetten AM. Regulation of peroxisome proliferator-activated receptor alpha-induced transactivation by the nuclear orphan receptor TAK1/TR4. J Biol Chem. 1998 May 1;273(18):10948-57. PMID:9556573
  4. ↑ 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
  5. ↑ Egawa D, Itoh T, Akiyama Y, Saito T, Yamamoto K. 17-OxoDHA Is a PPARalpha/gamma Dual Covalent Modifier and Agonist. ACS Chem Biol. 2016 Jul 1. PMID:27337155 doi:http://dx.doi.org/10.1021/acschembio.6b00338

5azt, resolution 3.45Å

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