We report on a stabilizer of the interaction between 14-3-3ζ and the Estrogen Receptor alpha (ERα). ERα is a driver in the majority of breast cancers and 14-3-3 proteins are negative regulators of this nuclear receptor, making the stabilization of this protein-protein interaction (PPI) an interesting strategy. The stabilizer (1) consists of three symmetric peptidic arms containing an arginine mimetic, previously described as the GCP motif. 1 stabilizes the 14-3-3ζ/ERα interaction synergistically with the natural product Fusicoccin-A and was thus hypothesized to bind to a different site. This is supported by computational analysis of 1 binding to the binary complex of 14-3-3 and an ERα-derived phosphopeptide. Furthermore, 1 shows selectivity towards 14-3-3ζ/ERα interaction over other 14-3-3 client-derived phosphomotifs. These data provide a solid support of a new binding mode for a supramolecular 14-3-3ζ/ERα PPI stabilizer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155037 | PMC |
| http://dx.doi.org/10.1002/anie.201914517 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Revealing the Active Components and Therapeutic Targets of Sanao Decoction against Chronic Obstructive Pulmonary Disease Using Quantitative Analysis of Multi-Components by Single Marker and Network Pharmacology.
J Chromatogr Sci
January 2025
School of Pharmacy, Shanghai University of Medicine and Health Sciences, 279 Zhouzhu Road, Pudong New District, Shanghai 201318, China.
As a traditional Chinese medicine, Sanao decoction (SAD) has been used to treat chronic obstructive pulmonary disease (COPD) for multi-years. However, the potential mechanism and targets for its effects of SAD remain unknown. The 94 components of SAD were identified by UPLC-LTQ-Orbitrap MS.
View Article and Find Full Text PDFIdentification, Clinical Values, and Prospective Pathway Signaling of Lipid Metabolism Genes in Epilepsy and AED Treatment.
Mol Neurobiol
January 2025
Department of Neurology, School of Medicine, Affiliated ZhongDa Hospital, Southeast University, Dingjiaqiao 87, Nanjing, 210009, Jiangsu, China.
The dysregulation of lipid metabolism has been associated with the etiology and progression of the neurological pathology. However, the roles of lipid metabolism and the molecular mechanism in epilepsy and the use of antiepileptic drugs (AEDs) are relatively understudied. Gene expression profiles of GSE143272 from blood samples were included for differential analysis, and the lipid metabolism-related differentially expressed genes (DEGs) were identified.
View Article and Find Full Text PDFExploring the mechanism of rosmarinic acid in the treatment of lung adenocarcinoma based on bioinformatics methods and experimental validation.
Discov Oncol
January 2025
Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine, No. 58, Yuelu District, Changsha, 410006, Hunan, China.
Objective: Rosmarinic acid (RosA) is a natural polyphenol compound that has been shown to be effective in the treatment of inflammatory disease and a variety of malignant tumors. However, its specific mechanism for the treatment of lung adenocarcinoma (LUAD) has not been fully elucidated. Therefore, this study aims to clarify the mechanism of RosA in the treatment of LUAD by integrating bioinformatics, network pharmacology and in vivo experiments, and to explore the potential of the active ingredients of traditional Chinese medicine in treating LUAD.
View Article and Find Full Text PDFSystematic qualitative proteome-wide analysis of lysine malonylation profiling in Platycodon grandiflorus.
Amino Acids
January 2025
College of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China.
In recent years, it was found that lysine malonylation modification can affect biological metabolism and play an important role in plant life activities. Platycodon grandiflorus, an economic crop and medicinal plant, had no reports on malonylation in the related literature. This study qualitatively introduces lysine malonylation in P.
View Article and Find Full Text PDFInsight into the structure, oligomerization, and the role in drug resistance of human UDP-glucuronosyltransferases.
Arch Toxicol
January 2025
Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Human UDP-glucuronosyltransferases (UGTs) are pivotal phase II metabolic enzymes facilitating the transfer of glucuronic acid from UDP-glucuronic acid (UDPGA) to various substrates. UGTs are classic type I transmembrane glycoproteins, mainly localized in the endoplasmic reticulum (ER) membrane. This review comprehensively explores UGTs, encompassing gene expression, functional characteristics, substrate specificity, and metabolic mechanisms.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!