Results 111 to 120 of about 692,160 (279)

Streptococcal Mannose Phosphotransferase System Component IID Is a Novel RANK‐Binding Osteoclastogenic Factor

Advanced Science, EarlyView.
Streptococcal mannose phosphotransferase system component IID (Man‐PTSIID) is identified as a novel RANK‐binding osteoclastogenic factor. By directly binding to RANK and activating NF‐κB independently of TLR2, Man‐PTSIID drives osteoclastogenesis and inflammatory bone destruction, uncovering an unexpected microbial mechanism underlying streptococcal ...
Chaeyeon Park, Yeongkag Kwon, Yeonjin Lim, Jeong Woo Park, Hyun Jung Ji, Dongwook Lee, Jueun Lee, Sung‐Ho Yun, Sungho Jeong, Ho Seong Seo, Kun Cho, Cheol‐Heui Yun, Ok‐Jin Park, Seung Hyun Han   +13 more
wiley   +1 more source

Molecular architecture responsible for specific inhibition of oncogenic PI3Kα mutants by RLY-2608 and STX-478

Acta Pharmaceutica Sinica B
Hotspot mutations in phosphoinositide 3-kinase alpha (PI3Kα), such as H1047R, E542K, and E545K, drive tumorigenesis across multiple cancer types. Orthosteric PI3Kα inhibitors are effective but have toxicity against wild-type PI3Kα, the emergence of ...
Xiao Liu, Yanyan Chen, Guanyi Li, Anqi Chen, Qingtong Zhou, Ming-Wei Wang   +5 more
doaj   +1 more source

Supramolecular Degraders: An Emerging Paradigm in Targeted Protein Degradation

Advanced Science, EarlyView.
Dynamic supramolecular assembly reshapes targeted protein degradation by coordinating modular degrader construction, delivery, functional integration, and intracellular assembly or activation across proteasomal, endosomal–lysosomal, and autophagy–lysosomal pathways.
Kongjun Liu, Xue Yuan, Yan Zhou, Rui Yuan, Shaocheng Xie, Yong Chen, Peiyi Wang, Jianmei Gao, Qihai Gong   +8 more
wiley   +1 more source

Evolutionarily Conserved Allosteric Communication in Protein Tyrosine Phosphatases [PDF]

, 2018
Protein tyrosine phosphatases (PTPs) are an important class of regulatory enzymes that exhibit aberrant activities in a wide range of diseases. A detailed mapping of allosteric communication in these enzymes could, thus, reveal the structural basis of ...
Michael K., Hjortness, Banumathi, Sankaran, Marco De, Vivo, Peter H., Zwart, Jerome, Fox, Akarawin, Hongdusit, Laura, Riccardi   +6 more
core   +2 more sources

Targeting β2‐Adrenergic Receptor Stability With Lycorine Reveals a Host‐Directed Pathway for Antiviral Defense Against Poxviruses

Advanced Science, EarlyView.
Chronic stress drives autophagy‐mediated β2‐AR degradation, impairing antiviral immunity and promoting poxvirus lethality. Lycorine directly stabilizes β2‐AR to restore host defense, suppress excessive inflammation and improve survival. ABSTRACT Psychological stress is a pervasive yet poorly understood modulator of infectious disease outcomes. Here, we
Xin Zhang, Shuqin Xu, Zixuan Zhang, Chenwen Wan, Xiaoqin Wang, Peihua Wang, Huini Yang, Tianxiao Huang, Yijia Yuan, Faiza Atique, Rui Yang, Yingli He, Zhijun Liu   +12 more
wiley   +1 more source

In Silico Mining of the Streptome Database for Hunting Putative Candidates to Allosterically Inhibit the Dengue Virus (Serotype 2) RdRp

Pharmaceuticals
Background/Objectives: In the last few decades, the dengue virus, a prevalent flavivirus, has demonstrated various epidemiological, economic, and health impacts around the world.
Alaa H. M. Abdelrahman, Gamal A. H. Mekhemer, Peter A. Sidhom, Tarad Abalkhail, Shahzeb Khan, Mahmoud A. A. Ibrahim   +5 more
doaj   +1 more source

A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints

Advanced Science, EarlyView.
ARESEC is a synthetic platform that reconstructs functional V(D)J recombination in HEK293T cells. By introducing RSS elements and co‐expressing RAG1/2 and TdT across all three antibody CDRs, it enables programmable junctional diversification and direct generation of high‐affinity variants targeting PD‐1/PD‐L1, overcoming the evolutionary constraints of
Wang Liu, Jun Yang, Yuhang Zhang, Xiaoli Xue   +3 more
wiley   +1 more source

Shifting the PPARγ conformational ensemble toward a transcriptionally repressive state improves covalent inhibitor efficacy

eLife
The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) regulates transcription in response to ligand binding at an orthosteric pocket within the ligand-binding domain (LBD).
Liudmyla Arifova, Brian S MacTavish, Zane Laughlin, Mithun Nag Karadi Girdhar, Jinsai Shang, Min-Hsuan Li, Xiaoyu Yu, Di Zhu, Theodore M Kamenecka, Douglas J Kojetin   +9 more
doaj   +1 more source

Targeting the PHB2–ACSL3 Lipid‐Remodeling Axis Overcomes Cisplatin Resistance by Restoring Ferroptosis in Gastric Cancer

Advanced Science, EarlyView.
ABSTRACT Platinum‐based chemotherapy resistance remains a major obstacle in gastric cancer (GC) treatment. Through integrated transcriptomic profiling of cisplatin‐resistant xenografts and pharmacogenomic interrogation of the NCI‐60 dataset, we identified Prohibitin‐2 (PHB2) as a previously unrecognized determinant of chemoresistance.
Liang Xu, Wanying Xiang, Xinyue Wang, Yue Pan, Jing Gao, Jiezhen Yang, Yufei Wang, Zhipu Zhu, Man Tong, Lei Jin, Yan Ye   +10 more
wiley   +1 more source

Corynoxine Inhibits Tumor Growth via Targeting NQO1 and Modulating the PTPA–NQO1/PP2A Switch to Activate PP2A

Advanced Science, EarlyView.
Corynoxine exerts potent broad‐spectrum anticancer activity by directly targeting NQO1. This interaction dissociates the oncogenic NQO1‐PTPA complex, releasing PTPA to robustly activate the tumor suppressor PP2A. Consequently, downstream Raf/MEK/ERK and PI3K/AKT signaling pathways are suppressed, downregulating c‐Myc and driving tumor regression ...
Guoqing Hou, Li Lin, Mengjie Xia, Ruohan Liang, Yueyue Zhang, Linna Du, Xuan Cao   +6 more
wiley   +1 more source