Results 81 to 90 of about 19,325 (262)

Mechanisms of activation and desensitization of full-length glycine receptor in lipid nanodiscs

Nature Communications, 2020
Glycinergic synapses play a central role in motor control and pain processing in the central nervous system. Here, authors present cryo-EM structures of the full-length glycine receptors (GlyRs) reconstituted into lipid nanodiscs in the unliganded ...
Arvind Kumar, Sandip Basak, Shanlin Rao, Yvonne Gicheru, Megan L. Mayer, Mark S. P. Sansom, Sudha Chakrapani   +6 more
doaj   +1 more source

Allosteric modulation of dextromethorphan binding sites

Neuropharmacology, 1987
The nonopioid antitussives dextromethorphan (DM), carbetapentane and caramiphen are efficacious anticonvulsant agents in the rat MES test. The findings presented strongly suggest the existence of a novel allosteric mechanism by which drugs acting at two different but interacting sites, exert their effects.
J M, Musacchio, M, Klein, L J, Santiago
openaire   +2 more sources

Systematically Engineering for Efficient Production of 3‐Methyl‐1‐Butanol in Escherichia coli

Advanced Science, EarlyView.
An integrated metabolic engineering strategy was established for high‐level 3‐methyl‐1‐butanol biosynthesis in Escherichia coli. Molecular dynamics‐guided semi‐rational engineering of dihydroxyacid dehydratase uncovered and relieved key catalytic bottlenecks, while adaptive laboratory evolution enhanced strain robustness.
Nanfei Geng, Hao Liu, Haolin Han, Meng Meng, Shaojie Wang, Tianwei Tan, Haijia Su   +6 more
wiley   +1 more source

Insights into the Allosteric Regulation of Human Hsp90 Revealed by NMR Spectroscopy

Biomolecules
Human heat shock protein 90 (Hsp90) is one of the most important chaperones that play a role in the late stages of protein folding. Errors in the process of the chaperone cycle can lead to diseases such as cancer and neurodegenerative diseases. Therefore,
Tjaša Goričan, Simona Golič Grdadolnik   +1 more
doaj   +1 more source

A Light-Controlled Allosteric Modulator Unveils a Role for mGlu4 Receptors During Early Stages of Ischemia in the Rodent Cerebellar Cortex

Frontiers in Cellular Neuroscience, 2018
Metabotropic glutamate receptors (mGlus) are G Protein coupled-receptors that modulate synaptic transmission and plasticity in the central nervous system.
Simon Bossi, Romain Helleringer, Micaela Galante, Ester Monlleó, Ana Trapero, Xavier Rovira, Hervé Daniel, Amadeu Llebaria, Heather McLean   +8 more
doaj   +1 more source

Development and Structural Characterization of UTE‐156, a Covalent Inhibitor of the VCP/p97 AAA+ ATPase

Advanced Science, EarlyView.
The AAA+ ATPase Valosin‐containing protein (VCP/p97) regulates protein homeostasis by unfolding ubiquitinated substrates. Here, we describe UTE‐156, a novel irreversible covalent inhibitor that modifies Cys522 in the D2 ATPase motor domain. Although its pharmacochemical limitations preclude immediate therapeutic use, UTE‐156 serves as a valuable ...
Daniela Tamayo‐Jaramillo, Subramanya Hegde, Xuan Jia, Kimberly Coffman, Hariprasad Vankayalapati, David Bearss, Kevin B. Jones, Alex W. Stark, Peter S. Shen   +8 more
wiley   +1 more source

Targeted Degradation of eEF2K by a Structure‐Guided PROTAC Strategy for the Treatment of Triple‐Negative Breast Cancer

Advanced Science, EarlyView.
This study developed an eEF2K‐targeting PROTAC, A6, that efficiently degrades eEF2K in TNBC cells, inhibiting tumor growth in vitro and in vivo. To enhance tumor‐specific delivery, we engineered A6@ZIF‐8, a pH‐sensitive nanocarrier, which improved drug accumulation at tumor sites, offering a promising therapeutic strategy for TNBC through targeted ...
Shijun Cao, Changxin Zhong, Shilong Jiang, Yungui Li, Yang Xi, Mingxuan Xiao, Ting Jiang, Xiaoya Wan, Zonglin Chen, Xiaohui Yu, Yan Cheng   +10 more
wiley   +1 more source

TRIM40 Drives Pathological Cardiac Hypertrophy and Heart Failure via Ubiquitination of PKN2

Advanced Science, EarlyView.
This study identifies the E3 ligase TRIM40 as a key driver of pathological cardiac hypertrophy. TRIM40 binds PKN2 via its B‐box domain and, through its C29‐dependent catalytic activity, mediates K63‐linked ubiquitination of PKN2. This modification enhances PKN2 phosphorylation at Ser815, thereby driving hypertrophy.
Risheng Zhao, Xiaoli Cui, Huizhu Du, Zhuoqun Wang, Chang Liu, Linxin Zhang, Jianing Qi, Di Yang, Hui Yu, Shuang Yan, Wei Liu, Haiming Sun, Mengyang Wang   +12 more
wiley   +1 more source

Automatically Defining Protein Words for Diverse Functional Predictions Based on Attention Analysis of a Protein Language Model

Advanced Science, EarlyView.
Understanding protein sequence–function relationships remains challenging due to poorly defined motifs and limited residue‐level annotations. An annotation‐agnostic framework is introduced that segments protein sequences into “protein words” using attention patterns from protein language models.
Hedi Chen, Jingrui Zhong, Xiaochun Zhang, Jingke Chen, Lin Guo, Xiaoliang Xiong, Xiaonan Zhang, Xiangyu Liu, Bailong Xiao, Boxue Tian   +9 more
wiley   +1 more source

Allosteric Modulation of αβδ GABAA Receptors [PDF]

Pharmaceuticals, 2010
GABAA receptors mediate the majority of the fast inhibition in the mature brain and play an important role in the pathogenesis of many neurological and psychiatric disorders. The αβδ GABAA receptor localizes extra- or perisynaptically and mediates GABAergic tonic inhibition.
openaire   +2 more sources