Structural highlights
3l0e is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Related: | 1p8d, 1pq6, 1pq9, 1upv |
| Gene: | NR1H2, LXRB, NER, UNR (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[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
[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). [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.[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Voegel JJ, Heine MJ, Tini M, Vivat V, Chambon P, Gronemeyer H. The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways. EMBO J. 1998 Jan 15;17(2):507-19. PMID:9430642 doi:10.1093/emboj/17.2.507
- ↑ 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
