Results 221 to 230 of about 3,750,504 (279)

NMDA receptor subunit‐dependent analysis of radiprodil inhibition in neonatal male rat substantia nigra dopaminergic neurons

British Journal of Pharmacology, EarlyView.
Abstract Background and Purpose Radiprodil is a GluN2B subunit selective NMDA receptor negative allosteric modulator which is currently under clinical investigation as a possible anti‐epileptic drug for paediatric use. Our goal was to investigate the inhibition of dopaminergic neuron NMDA responses by radiprodil.
Bangyuan Liu, Alasdair J. Gibb
wiley   +1 more source

The c‐Src inhibitor eCF506 diminishes opioid tolerance and reduces β‐arrestin2 recruitment

British Journal of Pharmacology, EarlyView.
Morphine activation of μ receptors causes tolerance through c‐Src activation and β‐arrestin2 recruitment. c‐Src inhibition or degradation reduces β‐arrestin2 recruitment, μ receptor endocytosis, while causing receptor upregulation, all likely contributing to reduced morphine tolerance.
Samuel Singleton, Fraser Nunn, Erika Lace, Álvaro Lorente‐Macías, Rachel Toth, Asier Unciti‐Broceta, Tim G. Hales   +6 more
wiley   +1 more source

The structural determinants of the bitopic binding mode of a negative allosteric modulator of the dopamine D₂ receptor. [PDF]

Biochem Pharmacol, 2018
Draper-Joyce CJ, Michino M, Verma RK, Klein Herenbrink C, Shonberg J, Kopinathan A, Scammells PJ, Capuano B, Thal DM, Javitch JA, Christopoulos A, Shi L, Lane JR.   +12 more
europepmc   +1 more source

Positive modulation of glucagon‐like peptide 1 (GLP‐1) receptor by endogenous haemorphins with implications in glucose metabolism and diabetes

British Journal of Pharmacology, EarlyView.
Haemorphins act on GLP‐1 receptor (GLP‐1R) activity and signalling in a positive allosteric manner. This leads to potentiated GLP‐1‐mediated activity and signalling, as well as insulin synthesis, which may have implications for glucose metabolism and, thereby, diabetes and obesity. (The graph was created in BioRender.com).
Farheen Badrealam Khan, Rwdah Mohamed Alameri, Yasir S. Raouf, Damien Maurel, Naiem Ahmad Wani, Anatoliy Shmygol, Irfa Anwar, Heng B. See, Elizabeth K. M. Johnstone, Elodie Dupuis, Eric Trinquet, Kevin D. G. Pfleger, Emilia Oueis, Mohammed Akli Ayoub   +13 more
wiley   +1 more source

Mitochondrial Morphology Dynamics Remodel Metabolism and Affect TKI Sensitivity in EGFR‐Mutated Lung Cancer

Cancer Science, EarlyView.
TKI treatment promotes mitochondrial fission and metabolic reprogramming toward oxidative phosphorylation in residual EGFR‐mutant lung cancer cells. Targeting this metabolic vulnerability restores TKI sensitivity and provides a promising strategy to overcome acquired resistance.
Yu Zhao, Yuqiang Liu, Mingxuan Xie, Zhiming Ye, Hong Huang, Maojin Yao, Feng Zhou, Jianzhu Zhao, Jun Tang   +8 more
wiley   +1 more source

PEG400 regulates Falcipain 2 activity through an allosteric mechanism

The FEBS Journal, EarlyView.
Falcipain‐2 can potentially be leveraged as a drug target due to its critical role as a haemoglobinase during the intra‐erythrocytic stage of Plasmodium falciparum. Here, we investigate the regulation of the proteolytic and haemoglobinase activity of falcipain‐2 in the presence of polyethylene glycol.
Bikram Nath, Subhoja Chakraborty, Sampa Biswas   +2 more
wiley   +1 more source

Resolving three GABA induced electrogenic events and GABA‐coupling stoichiometry for Na+ and Cl− in hGAT‐1

The FEBS Journal, EarlyView.
Using solid‐supported membrane electrophysiology, we resolved three electrogenic events during GABA transport by the human GAT‐1 transporter. A rapid occlusion step (E1) is followed by a GABA‐induced Na+ leak current (E2), which becomes prominent under steep Na+ gradients, and a slower current associated with Na+‐coupled GABA transport (E3 ...
Rocco Zerlotti, Maria Barthmes, Kim Cole, Anna Mondini, Jean‐François Rolland, Niels Fertig, Christine Ziegler, M. Gregor Madej, Andre Bazzone   +8 more
wiley   +1 more source

Structural insights into θ‐type carbonic anhydrases 3 and 4: Tuning the directionality of CO2 hydration in a diatom

The FEBS Journal, EarlyView.
θ‐CA3 from a marine diatom has an N‐terminal transmembrane helix and two homologous catalytic domains. The enzyme functions as a dimer, with active sites formed near the dimer interface. A bicarbonate ion binds on the symmetry axis of the dimer and forms hydrogen bonds with both monomers, thereby activating θ‐CA3 and tuning CO2 hydration activity ...
Hiroto Negoro, Atsuki Ohsawa, Ginga Shimakawa, Hideaki Tanaka, Yusuke Matsuda, Genji Kurisu   +5 more
wiley   +1 more source

Directional information flow in human frataxin defines allosteric pathways connecting the hydrophobic core to the iron‐binding ridge

The FEBS Journal, EarlyView.
Human frataxin deficiency causes Friedreich's ataxia, yet how iron‐binding events are communicated across the protein is unclear. Using transfer entropy analysis of molecular dynamics simulations, we identify buried hydrophobic core leucines (LEU136, LEU140) as the source of directional signaling toward the iron‐binding acidic ridge.
Kevser Kübra Kırboğa, Ecir Uğur Küçüksille   +1 more
wiley   +1 more source

Structures of the UBR4 complex reveal a giant arena to capture diverse substrates for ubiquitin chain elongation

The FEBS Journal, EarlyView.
This review summarizes recent structures of the UBR4 complex, a giant E4 ubiquitin ligase which recognizes proteins with pre‐existing ubiquitin modifications and marks them for degradation. The UBR4 complex uses a large arena lined with substrate interaction modules to select features on ubiquitinated substrates, such as the presence of N‐degrons or ...
Daniel B. Grabarczyk, Tim Clausen
wiley   +1 more source