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| | <StructureSection load='3l0e' size='340' side='right'caption='[[3l0e]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='3l0e' size='340' side='right'caption='[[3l0e]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3l0e]] is a 2 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=3L0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L0E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3l0e]] 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=3L0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L0E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G58:N-(2-CHLORO-6-FLUOROBENZYL)-1-METHYL-N-{[3-(METHYLSULFONYL)BIPHENYL-4-YL]METHYL}-1H-IMIDAZOLE-4-SULFONAMIDE'>G58</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1p8d|1p8d]], [[1pq6|1pq6]], [[1pq9|1pq9]], [[1upv|1upv]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G58:N-(2-CHLORO-6-FLUOROBENZYL)-1-METHYL-N-{[3-(METHYLSULFONYL)BIPHENYL-4-YL]METHYL}-1H-IMIDAZOLE-4-SULFONAMIDE'>G58</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR1H2, LXRB, NER, UNR ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3l0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l0e OCA], [https://pdbe.org/3l0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l0e RCSB], [https://www.ebi.ac.uk/pdbsum/3l0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l0e 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=3l0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l0e OCA], [https://pdbe.org/3l0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l0e RCSB], [https://www.ebi.ac.uk/pdbsum/3l0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l0e ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[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 == |
| - | [[https://www.uniprot.org/uniprot/NR1H2_HUMAN NR1H2_HUMAN]] Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity). [[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>
| + | [https://www.uniprot.org/uniprot/NR1H2_HUMAN NR1H2_HUMAN] Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gampe, R T]] | + | [[Category: Gampe Jr RT]] |
| - | [[Category: Activator]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Hlxr-beta]]
| + | |
| - | [[Category: Human liver x receptor-beta]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Sulfonamide modulator]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| Structural highlights
Function
NR1H2_HUMAN Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity).
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
Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.
Discovery of Tertiary Sulfonamides as Potent Liver X Receptor Antagonists.,Zuercher WJ, Buckholz RG, Campobasso N, Collins JL, Galardi CM, Gampe RT, Hyatt SM, Merrihew SL, Moore JT, Oplinger JA, Reid PR, Spearing PK, Stanley TB, Stewart EL, Willson TM J Med Chem. 2010 Mar 26. PMID:20345102[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zuercher WJ, Buckholz RG, Campobasso N, Collins JL, Galardi CM, Gampe RT, Hyatt SM, Merrihew SL, Moore JT, Oplinger JA, Reid PR, Spearing PK, Stanley TB, Stewart EL, Willson TM. Discovery of Tertiary Sulfonamides as Potent Liver X Receptor Antagonists. J Med Chem. 2010 Mar 26. PMID:20345102 doi:10.1021/jm901797p
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