6knr

Crystal structure of Estrogen-related receptor gamma ligand-binding domain with DN200699Crystal structure of Estrogen-related receptor gamma ligand-binding domain with DN200699

Structural highlights

6knr is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.804Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ERR3_HUMAN Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity).^[1] ^[2] ^[3]

Publication Abstract from PubMed

Estrogen-related receptor gamma (ERRgamma) is the NR3B subgroup of associated transcription factors. In this report, a new generation of a potent and selective ERRgamma inverse agonist (25) with good biocompatibility was proposed. We also explored the potential of the newly developed compound 25 in the PDTC model to expand the original indications from ATC. In addition, an X-ray crystallographic study of the ligand and ERRgamma co-complex showed that 25 completely binds to the target protein (PDB 6KNR). Its medicinal chemistry, including a distinctive structural study to in vivo results, denotes that 25 may be directed towards the development of a pivotal treatment for ERRgamma-related cancers.

An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer.,Kim J, Hwang H, Yoon H, Lee JE, Oh JM, An H, Ji HD, Lee S, Cha E, Ma MJ, Kim DS, Lee SJ, Kadayat TM, Song J, Lee SW, Jeon JH, Park KG, Lee IK, Jeon YH, Chin J, Cho SJ Eur J Med Chem. 2020 Jul 14;205:112501. doi: 10.1016/j.ejmech.2020.112501. PMID:32758860^[4]

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

References

↑ Hentschke M, Susens U, Borgmeyer U. Transcriptional ERRgamma2-mediated activation is regulated by sentrin-specific proteases. Biochem J. 2009 Apr 1;419(1):167-76. doi: 10.1042/BJ20081556. PMID:19067653 doi:10.1042/BJ20081556
↑ Tremblay AM, Wilson BJ, Yang XJ, Giguere V. Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif. Mol Endocrinol. 2008 Mar;22(3):570-84. Epub 2007 Dec 6. PMID:18063693 doi:me.2007-0357
↑ Greschik H, Wurtz JM, Sanglier S, Bourguet W, van Dorsselaer A, Moras D, Renaud JP. Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3. Mol Cell. 2002 Feb;9(2):303-13. PMID:11864604
↑ Kim J, Hwang H, Yoon H, Lee JE, Oh JM, An H, Ji HD, Lee S, Cha E, Ma MJ, Kim DS, Lee SJ, Kadayat TM, Song J, Lee SW, Jeon JH, Park KG, Lee IK, Jeon YH, Chin J, Cho SJ. An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer. Eur J Med Chem. 2020 Jul 14;205:112501. doi: 10.1016/j.ejmech.2020.112501. PMID:32758860 doi:http://dx.doi.org/10.1016/j.ejmech.2020.112501

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OCA

[1] Hentschke M, Susens U, Borgmeyer U. Transcriptional ERRgamma2-mediated activation is regulated by sentrin-specific proteases. Biochem J. 2009 Apr 1;419(1):167-76. doi: 10.1042/BJ20081556. PMID:19067653 doi:10.1042/BJ20081556

[2] Tremblay AM, Wilson BJ, Yang XJ, Giguere V. Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif. Mol Endocrinol. 2008 Mar;22(3):570-84. Epub 2007 Dec 6. PMID:18063693 doi:me.2007-0357

[3] Greschik H, Wurtz JM, Sanglier S, Bourguet W, van Dorsselaer A, Moras D, Renaud JP. Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3. Mol Cell. 2002 Feb;9(2):303-13. PMID:11864604

[4] Kim J, Hwang H, Yoon H, Lee JE, Oh JM, An H, Ji HD, Lee S, Cha E, Ma MJ, Kim DS, Lee SJ, Kadayat TM, Song J, Lee SW, Jeon JH, Park KG, Lee IK, Jeon YH, Chin J, Cho SJ. An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer. Eur J Med Chem. 2020 Jul 14;205:112501. doi: 10.1016/j.ejmech.2020.112501. PMID:32758860 doi:http://dx.doi.org/10.1016/j.ejmech.2020.112501

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