Kusal T G Samarasinghe,Craig M Crews
Kusal T G Samarasinghe
Protein homeostasis, or "proteostasis," is indispensable for a balanced, healthy environment within the cell. However, when natural proteostasis mechanisms are overwhelmed from excessive loads of dysregulated proteins, their accumulation ca...
Endogenous vitamin E metabolites mediate allosteric PPARγ activation with unprecedented co-regulatory interactions [0.03%]
内源性维生素E代谢物以前所未有的共调节相互作用介导异构PPARγ激活
Sabine Willems,Leonie Gellrich,Apirat Chaikuad et al.
Sabine Willems et al.
Vitamin E exhibits pharmacological effects beyond established antioxidant activity suggesting involvement of unidentified mechanisms. Here, we characterize endogenously formed tocopherol carboxylates and the vitamin E mimetic garcinoic acid...
Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2 [0.03%]
开发针对SARS-CoV-2半胱氨酸蛋白酶的高效和选择性抑制剂
Hengyue Shan,Jianping Liu,Jiali Shen et al.
Hengyue Shan et al.
The COVID-19 pandemic has been disastrous to society and effective drugs are urgently needed. The papain-like protease domain (PLpro) of SARS-CoV-2 (SCoV2) is indispensable for viral replication and represents a putative target for pharmaco...
Targeting SUMOylation dependency in human cancer stem cells through a unique SAE2 motif revealed by chemical genomics [0.03%]
基于化学基因组学发现的特异性SAE2修饰位点抑制人类癌症干细胞中的SUMO化依赖性
Yannick D Benoit,Ryan R Mitchell,Wenliang Wang et al.
Yannick D Benoit et al.
Natural products (NPs) encompass a rich source of bioactive chemical entities. Here, we used human cancer stem cells (CSCs) in a chemical genomics campaign with NP chemical space to interrogate extracts from diverse strains of actinomycete ...
Shanshan Duan,Michele Pagano
Shanshan Duan
Ubiquitylation, a highly regulated post-translational modification, controls many cellular pathways that are critical to cell homeostasis. Ubiquitin ligases recruit substrates and promote ubiquitin transfer onto targets, inducing proteasoma...
Specific inhibition of oncogenic RAS using cell-permeable RAS-binding domains [0.03%]
使用细胞穿透RAS结合域特异性抑制致癌RAS
Teiko Komori Nomura,Kazuki Heishima,Nobuhiko Sugito et al.
Teiko Komori Nomura et al.
Oncogenic RAS proteins, common oncogenic drivers in many human cancers, have been refractory to conventional small-molecule and macromolecule inhibitors due to their intracellular localization and the lack of druggable pockets. Here, we pre...
Rapid in vitro prototyping of O-methyltransferases for pathway applications in Escherichia coli [0.03%]
一种快速的体外方法在大肠杆菌中生成O-甲基转移酶用于途径应用
Kristina Haslinger,Thomas Hackl,Kristala L J Prather
Kristina Haslinger
O-Methyltransferases are ubiquitous enzymes involved in biosynthetic pathways for secondary metabolites such as bacterial antibiotics, human catecholamine neurotransmitters, and plant phenylpropanoids. While thousands of putative O-methyltr...
Expanding the arsenal of E3 ubiquitin ligases for proximity-induced protein degradation [0.03%]
用于邻近诱导蛋白降解的E3泛素连接酶库拓展
Aimo Kannt,Ivan Đikić
Aimo Kannt
Efficacy and selectivity of molecules inducing protein degradation depend on their affinity to the target protein but also on the type of E3 ubiquitin ligase that is recruited to trigger proteasomal degradation. While tremendous progress ha...
Discovery of a covalent inhibitor of heat shock protein 90 with antitumor activity that blocks the co-chaperone binding via C-terminal modification [0.03%]
一种通过C端修饰阻断辅分子结合的具有抗肿瘤活性的HSP90共价抑制剂的发现
Li Li,Nannan Chen,Dandan Xia et al.
Li Li et al.
Heat shock protein (Hsp90), a critical molecular chaperone that regulates the maturation of a large number of oncogenic client proteins, plays an essential role in the growth of neoplastic cells. Herein, DDO-6600 is identified to covalent m...
Haven't got a glue: Protein surface variation for the design of molecular glue degraders [0.03%]
无胶可牵：基于蛋白表面变构位点设计分子胶降解剂
Zuzanna Kozicka,Nicolas Holger Thomä
Zuzanna Kozicka
Molecular glue degraders are small, drug-like compounds that induce interactions between an E3 ubiquitin ligase and a target, which result in ubiquitination and subsequent degradation of the recruited protein. In recent years, serendipitous...