Results 81 to 90 of about 57,293 (304)

An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering

eLife, 2018
Allostery is an inherent feature of proteins, but it remains challenging to reveal the mechanisms by which allosteric signals propagate. A clearer understanding of this intrinsic circuitry would afford new opportunities to modulate protein function. Here,
Daniel A Keedy, Zachary B Hill, Justin T Biel, Emily Kang, T Justin Rettenmaier, José Brandão-Neto, Nicholas M Pearce, Frank von Delft, James A Wells, James S Fraser   +9 more
doaj   +1 more source

A Modular Biosensor Platform for the Detection of Plastic Monomers and the Engineering of Promiscuous Amidases Toward Challenging Substrates

Advanced Science, EarlyView.
A luciferase is used as biosensor for aldehydes, produced enzymatically from different monomeric building blocks of plastics like polyurethanes (PUs). The screening platform is used to monitor esterase, amidase, and urethanase activity and to guide the selection of enzyme variants with improved hydrolytic activities toward difficult to hydrolyze ...
Ina Somvilla, Hannah Meier, Florian Oehlschläger, Hannes Meinert, Lena Koch, Patrick Ihrle, Katharina M. Mehnert, Morten Flieger, Jonas Boß, Marco Seifert, Dominique Böttcher, Uwe T. Bornscheuer, Thomas Bayer   +12 more
wiley   +1 more source

Engineering Fluoroacetate Dehalogenase by Growth‐Based Selections on Non‐Natural Organofluorides

Angewandte Chemie, EarlyView.
We present a high‐throughput selection system to engineer fluoroacetate dehalogenases (FAcDs). By challenging E. coli populations that produce diverse FAcD libraries to grow on non‐natural organofluorides as their sole carbon source, we isolated a panel of FAcD variants with improved activity and altered substrate specificity.
Suzanne C. Jansen, Pauline van Beers, Clemens Mayer   +2 more
wiley   +2 more sources

Generating Dynamic Structures Through Physics‐Based Sampling of Predicted Inter‐Residue Geometries

Advanced Science, EarlyView.
While static structure prediction has been revolutionized, modeling protein dynamics remains elusive. trRosettaX2‐Dynamics is presented to address this challenge. This framework leverages a Transformer‐based network to predict inter‐residue geometric constraints, guiding conformation generation via physics‐based iterative sampling. The resulting method
Chenxiao Xiang, Wenkai Wang, Zhenling Peng, Jianyi Yang   +3 more
wiley   +1 more source

Discovery of a First‐in‐Class Covalent Allosteric SHP1 Inhibitor with Immunotherapeutic Activity

Angewandte Chemie, EarlyView.
A covalent allosteric inhibitor M029 was discovered for SHP1, a novel target for immunotherapy. M029 binds to a cryptic Cys remote from the active site, exhibits robust target engagement, and blocks tumor progression by stimulating antitumor immune response.
Zihan Qu, Frederick Nguele Meke, Zheng Zhang, Aaron D. Krabill, Christine S. Muli, Brenson A. Jassim, Jiajun Dong, Quyen D. Nguyen, Yunpeng Bai, Jinyue Li, Yiming Miao, Bardia Asadi, Levi M. Johnson, Jinmin Miao, Darci J. Trader, W. Andy Tao, Zhong‐Yin Zhang   +16 more
wiley   +2 more sources

Ligand‐Induced Electronic Response Enables Predictive QM/MM Simulations

Advanced Science, EarlyView.
Quantum mechanics/molecular mechanics (QM/MM) simulations are powerful tools for modeling complex molecular systems; however, their predictability has been constrained by the ambiguous definition of the QM region. An electronically informed protocol is introduced that defines QM regions by quantifying guest‐induced orbital shifts and charge ...
Nichika Ozawa, Nahoko Kuroki, Hirotoshi Mori   +2 more
wiley   +1 more source

Mechanistic Insights into the Mechanism of Allosteric Inhibition of Ubiquitin-Specific Protease 7 (USP7)

Biomolecules
Ubiquitin-specific protease 7 (USP7), a deubiquitinase enzyme responsible for removing ubiquitin (Ub) from target proteins, plays a crucial role in oncogenic pathways and has been implicated in various human diseases.
Xuebin Wang, Ning Liu, Nuan Li, Shaoyong Lu, Zongtao Chai   +4 more
doaj   +1 more source

All Nanozyme‐Based Cascade Reactions for Biomedical Applications: from Self‐Cascading Nanozyme to Immobilized Cascade Nanozyme

Advanced Science, EarlyView.
This review introduces the development and classification of all‐nanozyme cascade reaction systems, highlighting mechanistic insights and research methods for understanding catalytic features and design principles. It provides detailed classifications, surveys recent applications in biosensing and therapy, and discusses the challenges that all‐nanozyme
Caixia Zhu, Congcong Jiang, Hian Kee Lee, Yuanjian Zhang, Sheng Tang   +4 more
wiley   +1 more source

Dynamic regulation of phenylalanine hydroxylase

Pteridines, 2014
Phenylalanine hydroxylase (PAH) is the key enzyme in phenylalanine metabolism, catalyzing its oxidative breakdown to tyrosine. Its function in the committed step of amino acid metabolism requires strict regulation. Thus, several regulatory mechanisms are
Fuchs Julian E., Fuchs Dietmar, Liedl Klaus R.   +2 more
doaj   +1 more source

NADH‐Reductive Stress Induced by Dihydrolipoamide Dehydrogenase Activation Contributes to Cuproptosis

Advanced Science, EarlyView.
This study demonstrates a cuproptosis mechanism involving nicotinamide adenine dinucleotide (NADH)‐reductive stress in neural cells. Copper activates dihydrolipoamide dehydrogenase under mitochondrial pH, accumulating NADH. Copper also induces mitochondrial permeability transition pore opening, facilitating NADH translocation to the cytosol and ...
Si‐Yi Zhang, Xing‐Hua Ren, Cheng‐Hong Zhang, Zhan‐You Wang   +3 more
wiley   +1 more source