Assignment of the orphan nuclear receptor Nurr1 by NMR

被引:10
作者
Michiels, Paul [1 ]
Atkins, Karen [2 ]
Ludwig, Christian [2 ]
Whittaker, Sara [2 ]
van Dongen, Maria [1 ]
Guenther, Ulrich [2 ]
机构
[1] Solvay Pharmaceut Res Labs, Hannover, Germany
[2] Univ Birmingham, Inst Canc Sci, Birmingham B15 2TT, W Midlands, England
基金
英国惠康基金;
关键词
Orphan nuclear receptor; NMR; Nurr1; Parkinson's disease; NR4A nuclear receptors; LIGAND-BINDING DOMAIN; PARKINSONS-DISEASE; RXR-ALPHA; EXPRESSION; RESONANCE;
D O I
10.1007/s12104-010-9210-4
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
The orphan nuclear receptor Nurr1 has been implicated in a number of conditions including Parkinson's disease and Schizophrenia. As such, it is of interest to study its interactions with other proteins, possibly mediated by small molecules, considering possible use as a drug target. We produced H-2, N-15, C-13 labelled-Nurr1 to generate the backbone amide NH, carbonyl C', C-alpha and C-beta assignments. About 84.0% of residues could be assigned. Most of the 37 missing assignments fall in 3 regions of the protein. Two of these surround a putative ligand-binding region of Nurr1, suggesting that this region of the protein is flexible, despite the ligand-binding pocket being filled with hydrophobic side-chains from residues surrounding the ligand binding pocket.
引用
收藏
页码:101 / 105
页数:5
相关论文
共 50 条
[21]   Orphan nuclear receptor Nurr1 directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell-specific manner [J].
Kim, KS ;
Kim, CH ;
Hwang, DY ;
Seo, H ;
Chung, SM ;
Hong, SJ ;
Lim, JK ;
Anderson, T ;
Isacson, O .
JOURNAL OF NEUROCHEMISTRY, 2003, 85 (03) :622-634
[22]   Regulation of GTP cyclohydrolase I expression by orphan receptor Nurr1 in cell culture and in vivo [J].
Gil, Minchan ;
McKinney, Cushla ;
Lee, Mi Kyeong ;
Eells, Jeffrey B. ;
Phyillaier, Marcia A. ;
Nikodem, Vera M. .
JOURNAL OF NEUROCHEMISTRY, 2007, 101 (01) :142-150
[23]   Activation of Peroxisome Proliferator-Activated Receptor-α Increases the Expression of Nuclear Receptor Related 1 Protein (Nurr1) in Dopaminergic Neurons [J].
Carl G. Gottschalk ;
Avik Roy ;
Malabendu Jana ;
Madhuchhanda Kundu ;
Kalipada Pahan .
Molecular Neurobiology, 2019, 56 :7872-7887
[24]   Activation of Peroxisome Proliferator-Activated Receptor-α Increases the Expression of Nuclear Receptor Related 1 Protein (Nurr1) in Dopaminergic Neurons [J].
Gottschalk, Carl G. ;
Roy, Avik ;
Jana, Malabendu ;
Kundu, Madhuchhanda ;
Pahan, Kalipada .
MOLECULAR NEUROBIOLOGY, 2019, 56 (11) :7872-7887
[25]   Nurr1 modulators - a patent review (2019-present) [J].
Egner, Markus ;
Merk, Daniel .
EXPERT OPINION ON THERAPEUTIC PATENTS, 2025,
[26]   Orphan nuclear receptor Nurr1 induces neuron differentiation from embryonic cortical precursor cells via an extrinsic paracrine mechanism [J].
Bae, Eun-Ji ;
Lee, Hyun-Seob ;
Park, Chang-Hwan ;
Lee, Sang-Hun .
FEBS LETTERS, 2009, 583 (09) :1505-1510
[27]   Nurr1 Expression and Its Modulation in Microglia [J].
Fan, Xiaolan ;
Luo, Guangrui ;
Ming, Ming ;
Pu, Pu ;
Li, Liang ;
Yang, Dehua ;
Le, Weidong .
NEUROIMMUNOMODULATION, 2009, 16 (03) :162-170
[28]   Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain [J].
Sakurada, K ;
Ohshima-Sakurada, M ;
Palmer, TD ;
Gage, FH .
DEVELOPMENT, 1999, 126 (18) :4017-4026
[29]   Nurr1 transcriptionally regulates the expression of α-synuclein [J].
Yang, Yan Xiang ;
Latchman, David S. .
NEUROREPORT, 2008, 19 (08) :867-871
[30]   Hydroxychloroquine antiparkinsonian potential: Nurr1 modulation versus autophagy inhibition [J].
Hedya, Shireen A. ;
Safar, Marwa M. ;
Bahgat, Ashraf K. .
BEHAVIOURAL BRAIN RESEARCH, 2019, 365 :82-88