| Structural highlights
5a5n is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Related: | 5a5o, 5a5p, 5a5q, 5a5r, 5a5s |
| Activity: | Adenosinetriphosphatase, with EC number 3.6.1.3 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ATAD2_HUMAN] May be a transcriptional coactivator of the nuclear receptor ESR1 required to induce the expression of a subset of estradiol target genes, such as CCND1, MYC and E2F1. May play a role in the recruitment or occupancy of CREBBP at some ESR1 target gene promoters. May be required for histone hyperacetylation. Involved in the estrogen-induced cell proliferation and cell cycle progression of breast cancer cells.[1]
Publication Abstract from PubMed
Overexpression of ATAD2 (ATPase family, AAA domain containing 2) has been linked to disease severity and progression in a wide range of cancers, and is implicated in the regulation of several drivers of cancer growth. Little is known of the dependence of these effects upon the ATAD2 bromodomain, which has been categorized as among the least tractable of its class. The absence of any potent, selective inhibitors limits clear understanding of the therapeutic potential of the bromodomain. Here, we describe the discovery of a hit from a fragment-based targeted array. Optimization of this produced the first known micromolar inhibitors of the ATAD2 bromodomain.
Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors.,Demont EH, Chung CW, Furze RC, Grandi P, Michon AM, Wellaway C, Barrett N, Bridges AM, Craggs PD, Diallo H, Dixon DP, Douault C, Emmons AJ, Jones EJ, Karamshi BV, Locke K, Mitchell DJ, Mouzon BH, Prinjha RK, Roberts AD, Sheppard RJ, Watson RJ, Bamborough P J Med Chem. 2015 Jul 9. PMID:26155854[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zou JX, Revenko AS, Li LB, Gemo AT, Chen HW. ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERalpha, is required for coregulator occupancy and chromatin modification. Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18067-72. Epub 2007 Nov 12. PMID:17998543 doi:http://dx.doi.org/10.1073/pnas.0705814104
- ↑ Demont EH, Chung CW, Furze RC, Grandi P, Michon AM, Wellaway C, Barrett N, Bridges AM, Craggs PD, Diallo H, Dixon DP, Douault C, Emmons AJ, Jones EJ, Karamshi BV, Locke K, Mitchell DJ, Mouzon BH, Prinjha RK, Roberts AD, Sheppard RJ, Watson RJ, Bamborough P. Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors. J Med Chem. 2015 Jul 9. PMID:26155854 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00772
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