1zdu

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Current revision (09:03, 14 February 2024) (edit) (undo)
 
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<StructureSection load='1zdu' size='340' side='right'caption='[[1zdu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='1zdu' size='340' side='right'caption='[[1zdu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[1zdu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZDU FirstGlance]. <br>
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<table><tr><td colspan='2'>[[1zdu]] 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=1ZDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZDU FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P3A:PHOSPHATIDYLGLYCEROL-PHOSPHOGLYCEROL'>P3A</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1zdt|1zdt]]</div></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=P3A:PHOSPHATIDYLGLYCEROL-PHOSPHOGLYCEROL'>P3A</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></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=1zdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zdu OCA], [https://pdbe.org/1zdu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zdu RCSB], [https://www.ebi.ac.uk/pdbsum/1zdu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zdu 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=1zdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zdu OCA], [https://pdbe.org/1zdu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zdu RCSB], [https://www.ebi.ac.uk/pdbsum/1zdu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zdu ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
 
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[[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 ==
== Function ==
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[[https://www.uniprot.org/uniprot/NR5A2_HUMAN NR5A2_HUMAN]] Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development. [[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>
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[https://www.uniprot.org/uniprot/NR5A2_HUMAN NR5A2_HUMAN] Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=1zdu ConSurf].
</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=1zdu ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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Steroidogenic factor-1 (SF-1) and liver receptor homologue-1 (LRH-1) belong to the fushi tarazu factor 1 subfamily of nuclear receptors. SF-1 is an essential factor for sex determination during development and regulates adrenal and gonadal steroidogenesis in the adult, whereas LRH-1 is a critical factor for development of endodermal tissues and regulates cholesterol and bile acid homeostasis. Regulatory ligands are unknown for SF-1 and LRH-1. A reported mouse LRH-1 structure revealed an empty pocket in a region commonly occupied by ligands in the structures of other nuclear receptors, and pocket-filling mutations did not alter the constitutive activity observed. Here we report the crystal structures of the putative ligand-binding domains of human SF-1 at 2.1-A resolution and human LRH-1 at 2.5-A resolution. Both structures bind a coactivator-derived peptide at the canonical activation-function surface, thus adopting the transcriptionally activating conformation. In human LRH-1, coactivator peptide binding also occurs to a second site. We discovered in both structures a phospholipid molecule bound in a pocket of the putative ligand-binding domain. MS analysis of the protein samples used for crystallization indicated that the two proteins associate with a range of phospholipids. Mutations of the pocket-lining residues reduced the transcriptional activities of SF-1 and LRH-1 in mammalian cell transfection assays without affecting their expression levels. These results suggest that human SF-1 and LRH-1 may be ligand-binding receptors, although it remains to be seen if phospholipids or possibly other molecules regulate SF-1 or LRH-1 under physiological conditions.
 
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The crystal structures of human steroidogenic factor-1 and liver receptor homologue-1.,Wang W, Zhang C, Marimuthu A, Krupka HI, Tabrizizad M, Shelloe R, Mehra U, Eng K, Nguyen H, Settachatgul C, Powell B, Milburn MV, West BL Proc Natl Acad Sci U S A. 2005 May 24;102(21):7505-10. Epub 2005 May 16. PMID:15897460<ref>PMID:15897460</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 1zdu" style="background-color:#fffaf0;"></div>
 
==See Also==
==See Also==
*[[Liver receptor homolog-1|Liver receptor homolog-1]]
*[[Liver receptor homolog-1|Liver receptor homolog-1]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Eng, K]]
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[[Category: Eng K]]
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[[Category: Krupka, H I]]
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[[Category: Krupka HI]]
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[[Category: Marimuthu, A]]
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[[Category: Marimuthu A]]
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[[Category: Mehra, U]]
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[[Category: Mehra U]]
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[[Category: Milburn, M V]]
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[[Category: Milburn MV]]
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[[Category: Nguyen, H]]
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[[Category: Nguyen H]]
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[[Category: Powell, B]]
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[[Category: Powell B]]
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[[Category: Settachatgul, C]]
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[[Category: Settachatgul C]]
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[[Category: Shelloe, R]]
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[[Category: Shelloe R]]
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[[Category: Tabrizizad, M]]
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[[Category: Tabrizizad M]]
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[[Category: Wang, W]]
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[[Category: Wang W]]
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[[Category: West, B L]]
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[[Category: West BL]]
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[[Category: Zhang, C]]
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[[Category: Zhang C]]
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[[Category: Liver receptor homologue-1]]
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[[Category: Lrh-1]]
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[[Category: Nuclear receptor]]
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[[Category: Phosphatidylethanolamine]]
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[[Category: Phospholipid]]
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[[Category: Transcription]]
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Current revision

The Crystal Structure of Human Liver Receptor Homologue-1

PDB ID 1zdu

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