3PCU

Crystal structure of human retinoic X receptor alpha ligand-binding domain complexed with LX0278 and SRC1 peptide

Summary for 3PCU

• Entry DOI: 10.2210/pdb3pcu/pdb
• Descriptor: Retinoic acid receptor RXR-alpha, Nuclear receptor coactivator 2, 2-[(2S)-6-(2-methylbut-3-en-2-yl)-7-oxo-2,3-dihydro-7H-furo[3,2-g]chromen-2-yl]propan-2-yl acetate, ... (4 entities in total)
• Functional Keywords: nuclear receptor rxralpha, ligand-binding domain, transcription-transcription regulator complex, transcription/transcription regulator
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P19793 Q15596
• Total number of polymer chains: 2
• Total formula weight: 27400.85

Authors

Zhang, H.,Zhang, Y.,Shen, H.,Chen, J.,Li, C.,Chen, L.,Hu, L.,Jiang, H.,Shen, X. (deposition date: 2010-10-22, release date: 2011-11-16, Last modification date: 2023-11-01)

Primary citation

Zhang, Y.,Zhang, H.,Yao, X.G.,Shen, H.,Chen, J.,Li, C.,Chen, L.,Zheng, M.,Ye, J.,Hu, L.,Shen, X.,Jiang, H.
(+)-Rutamarin as a Dual Inducer of Both GLUT4 Translocation and Expression Efficiently Ameliorates Glucose Homeostasis in Insulin-Resistant Mice.
Plos One, 7:e31811-e31811, 2012

PubMed Abstract: Glucose transporter 4 (GLUT4) is a principal glucose transporter in response to insulin, and impaired translocation or decreased expression of GLUT4 is believed to be one of the major pathological features of type 2 diabetes mellitus (T2DM). Therefore, induction of GLUT4 translocation or/and expression is a promising strategy for anti-T2DM drug discovery. Here we report that the natural product (+)-Rutamarin (Rut) functions as an efficient dual inducer on both insulin-induced GLUT4 translocation and expression. Rut-treated 3T3-L1 adipocytes exhibit efficiently enhanced insulin-induced glucose uptake, while diet-induced obese (DIO) mice based assays further confirm the Rut-induced improvement of glucose homeostasis and insulin sensitivity in vivo. Subsequent investigation of Rut acting targets indicates that as a specific protein tyrosine phosphatase 1B (PTP1B) inhibitor Rut induces basal GLUT4 translocation to some extent and largely enhances insulin-induced GLUT4 translocation through PI3 kinase-AKT/PKB pathway, while as an agonist of retinoid X receptor α (RXRα), Rut potently increases GLUT4 expression. Furthermore, by using molecular modeling and crystallographic approaches, the possible binding modes of Rut to these two targets have been also determined at atomic levels. All our results have thus highlighted the potential of Rut as both a valuable lead compound for anti-T2DM drug discovery and a promising chemical probe for GLUT4 associated pathways exploration.

PubMed: 22384078
DOI: 10.1371/journal.pone.0031811

Experimental method

X-RAY DIFFRACTION (2 Å)