Results 121 to 130 of about 3,750,504 (279)

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

Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator

Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative of the metabotropic glutamate type
Bresolí-Obach, Roger, Font, Joan, López-Cano, Marc, Llebaria Soldevila, Amadeu, Ciruela Alférez, Francisco, Scarselli, Pamela, Goudet, Cyril, Nonell, S. (Santi), Catena, Juanlo, Malhaire, Fanny, Di Pietro, Paola, Battaglia, Giuseppe, Giraldo, Jesús, Pin, Jean-Philippe, Nicoletti, Ferdinando, Rovira, Xavier, Fernández Dueñas, Víctor, Notartomaso, Serena   +17 more
core   +1 more source

Concentration dependence of the interaction of two allosteric modulators that compete for the same allosteric site.

, 2019
Upper row, simulation of tracer binding (ordinate) in the presence of two allosteric modulators A and B competing for the same allosteric site, where α is either less than one (left) or greater than one (right) and B is negative allosteric modulator ...
Esam E. El-Fakahany (339452), Alena Randáková (339451), Jan Jakubík (339449), Vladimír Doležal (339453)   +3 more
core   +1 more source

Macrophage RSAD2 Couples mtDNA Synthesis With a Self‐Amplifying Inflammatory Circuit to Orchestrate Tissue Repair

Advanced Science, EarlyView.
Macrophage RSAD2 dually regulates CMPK2—the rate‐limiting enzyme for mitochondrial DNA synthesis—by suppressing its ubiquitination and promoting its phosphorylation via Csnk2a2 recruitment. This amplifies mtDNA production, which simultaneously activates a cGAS‐STING‐IRF3‐RSAD2 feedforward loop and the NLRP3 inflammasome, driving a self‐sustaining ...
Haomiao Yuan, Shukui Du, Chunfei Li, Xinjie Li, Shuyang Mu, Anran Qu, Hengxu Yan, Chongchong Xu, Jinnong Yang, Jingkai Sun, Yijun Wang, Jiayang Xiao, Fuyuan Zhang, Linlin Wang, Tiegang Li, Rui Zhao, Dawei Guan   +16 more
wiley   +1 more source

DyProL: Dynamic Ensemble Representation Learning for Protein–Nucleic Acid Binding Site Prediction

Advanced Science, EarlyView.
Protein function is represented as a dynamic conformational ensemble rather than a single static structure. A multi‐conformation geometric attention framework aligns, clusters, and learns representative states to capture residue‐ and ensemble‐level signals. Integrating structural dynamics improves interpretable protein‐NA binding prediction and reveals
Pengpai Li, Yiman Liu, Liya Liang, Rongming Liu   +3 more
wiley   +1 more source

Reversible, Chemically Gated FRET via Ligand‐Activated Acceptors

Advanced Science, EarlyView.
Fluorogen binding turns the compact FAST tag into a tunable FRET acceptor, with ligand chemistry programming spectral overlap and excited‐state lifetimes. Fluorescence‐lifetime imaging reads out energy transfer through the shortened donor lifetime, while simply adding or washing out the dye switches FRET on and off, reversibly mapping the supramodular ...
Nivedita Singh, Smruti Ranjan Nayak, Sanjay Kumar Mohanty, Aishwarya Hanumantharaju, Amala Shaju, Mini Jose, Aravind Penmatsa, Deepak Nair   +7 more
wiley   +1 more source

Structural Dynamics and Allosteric Signaling in Ionotropic Glutamate Receptors [PDF]

, 2013
Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate excitatory neurotransmission events in the central nervous system. All distinct classes of iGluRs (AMPA, NMDA, Kainate) are composed of an N-terminal domain (NTD) and a ...
Dutta, Anindita
core  

Structural Basis of Lymphangiogenic Receptor VEGFR‐3 Activation Mediated by Distinctive Clustering of the Ligand–Receptor Complex

Advanced Science, EarlyView.
VEGF‐C and its receptor VEGFR‐3 are critical for lymphangiogenesis. Cryo‐EM structures of the VEGFR‐3/VEGF‐C ectodomain complex reveal a canonical 2:2 ligand–receptor hetero‐tetramer that further assembles into higher‐order clusters beyond simple receptor dimerization.
Ryeongeun Cho, Jinsook Ahn, Jimin Yang, Dong Sun Lee, Gahi Hong, Sangkyu Lee, Ho Min Kim   +6 more
wiley   +1 more source

Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors

Nature Communications
Allosteric modulation is a central mechanism for metabolic regulation but has yet to be described for a gut microbiota-host interaction. Phenylacetylglutamine (PAGln), a gut microbiota-derived metabolite, has previously been clinically associated with ...
Prasenjit Prasad Saha, Valentin Gogonea, Wendy Sweet, Maradumane L. Mohan, Khuraijam Dhanachandra Singh, James T. Anderson, Deepthi Mallela, Conner Witherow, Niladri Kar, Kate Stenson, Terri Harford, Michael A. Fischbach, J. Mark Brown, Sadashiva S. Karnik, Christine S. Moravec, Joseph A. DiDonato, Sathyamangla Venkata Naga Prasad, Stanley L. Hazen   +17 more
doaj   +1 more source

An Extracellular Pore‑Targeting Peptide Defines a Designable Allosteric Site in TRPV2

Advanced Science, EarlyView.
Structure‐guided peptide engineering yields Depiv2, a highly potent and subtype‐selective TRPV2 inhibitor that binds to the extracellular pore and remodels it into a closed, non‐conductive state. Depiv2 suppresses pathological cardiac hypertrophy, establishing the TRPV2 outer pore as a designable interface for selective peptide modulation.
Aiqin Zhu, Hongkun Wang, Jiawei Wang, Xiaolu Liu, Aerziguli Aierken, Lizhen Xu, Ping Liang, Fan Yang   +7 more
wiley   +1 more source