Article
Biochemistry & Molecular Biology
Ma Yangchun, Yang Wenyu, Zhou Liang, Li Lipeng, Wu Jingwei, Li Weiya, Du Shan, Ma Ying, Wang Runling
Summary: Studies have shown that the dual allosteric targeted inhibition mechanism of SHP2 involves the combination of SHP099 and SHP844 to inhibit the pharmacological pathway in cells and prevent the substrate from entering the catalytic site.
MOLECULAR DIVERSITY
(2022)
Review
Pharmacology & Pharmacy
Oscar Diaz, Victor Martin, Pedro Renault, David Romero, Antoni Guillamon, Jesus Glraldo
Summary: Allosteric modulators play a crucial role in drug discovery by regulating the binding and function of endogenous ligands. They offer advantages over orthosteric ligands, with binding cooperativity being a typical pharmacological parameter in allosteric modulation. By decomposing this property into kinetic parameters, a relationship for cooperativity rate constant parameters has been derived using two reference models. This assessment can aid in understanding unexpected experimental results and guide further investigations in the field of allosteric modulation.
DRUG DISCOVERY TODAY
(2023)
Review
Pharmacology & Pharmacy
Veronica Casado-Anguera, Vicent Casado
Summary: This review summarizes both classical and non-classical allosterism, focusing on G protein-coupled receptor (GPCR) oligomers as a paradigm. The study of these new non-classical allosteric sites will expand the diversity of allosteric control and increase the therapeutic potential of allosterism.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Review
Biochemistry & Molecular Biology
Guanya Li, Dunhui Li, Tao Wang, Shanping He
Summary: CAD is a multifunctional protein involved in the initial steps of pyrimidine nucleotide synthesis, playing a central role in the synthesis of nucleic acids, active intermediates, and cell membranes. Deregulation of CAD-related pathways or CAD mutations can lead to various diseases such as cancer, neurological disorders, and inherited metabolic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Xiaoting Liu, Caijing Han, Li Fang, Zhanqing Fan, Yanan Wang, Xin Gao, Junhua Shi, Weihong Min
Summary: The study successfully increased enzyme activity by mutating key allosteric regulatory sites. Molecular dynamics simulations revealed that Lys inhibits enzymatic reaction by affecting protein conformation.
Article
Multidisciplinary Sciences
Leo Bellin, Francisco Del Cano-Ochoa, Adrian Velazquez-Campoy, Torsten Moehlmann, Santiago Ramon-Maiques
Summary: ATC in plants is regulated by feedback inhibition via UMP, which binds to a plant-specific loop and blocks the active site, competing with substrate binding. This unique regulatory mechanism of plant ATCs could be utilized to modulate de novo pyrimidine synthesis and plant growth.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Elena Shanina, Sakonwan Kuhaudomlarp, Kanhaya Lal, Peter H. Seeberger, Anne Imberty, Christoph Rademacher
Summary: Carbohydrate-binding proteins, specifically lectins, are promising targets in drug discovery for combating antimicrobial resistance, yet non-carbohydrate drug-like inhibitors are still lacking. A druggable pocket in a beta-propeller lectin from Burkholderia ambifaria has been identified as a potential target for allosteric inhibitors. Future drug-discovery efforts focusing on small molecule inhibitors could benefit from targeting allosteric sites in lectins to combat antibiotic-resistant pathogens.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biology
James W. McCormick, Marielle A. X. Russo, Samuel Thompson, Aubrie Blevins, Kimberly A. Reynolds
Summary: Through studying the impact of allosteric mutations, it was found that a small number of mutations have significant effects on allostery, with most disrupting mutations localized to specific regions and enhancing mutations distributed widely and enriched on the protein surface. Combining multiple enhancing mutations can lead to near-additive improvements in dynamic range.
Article
Biology
John W. Biddle, Rosa Martinez-Corral, Felix Wong, Jeremy Gunawardena
Summary: Integration of binding information in cells relies on higher-order cooperativities instead of pairwise cooperativities, which is achieved through allostery and dynamic conformational ensembles. This mechanism of information integration can be implemented without energy expenditure, providing a rigorous foundation for analyzing binding integration through allostery in eukaryotic gene regulation.
Article
Chemistry, Physical
Dongyu Liu, Devan Solanki, Eli Stavitski, Mingtao Li, Shu Hu, Victor S. Batista, Ke R. Yang
Summary: This study demonstrates that alloyed TiO2 electrodes with subsurface redox-active transition metals can enable water oxidation to H2O2 at low overpotentials. The first-row transition metals (Cr, Mn, Fe, and Co) act as reservoirs of oxidizing equivalents that couple to substrate binding sites. The distinct sites for substrate binding and redox state transitions reduce the overpotential of the critical first step of water oxidation and enhance the selectivity for H2O2.
ACS APPLIED ENERGY MATERIALS
(2023)
Article
Chemistry, Medicinal
Xiaochen Du, Vidhisha Sonawane, Bidong Zhang, Chao Wang, Bram de Ruijter, Alexander S. S. Domling, Norbert Reiling, Matthew R. Groves
Summary: Aspartate transcarbamoylase (ATCase) is a target for suppressing cell proliferation in E. coli, human cells and the malarial parasite. This study aimed to test if a library of ATCase inhibitors developed for malarial ATCase (PfATCase) also inhibit the tubercular ATCase and show similar effects on cellular proliferation. Screening of 70 compounds revealed 10 inhibitors with single-digit micromolar inhibition in vitro, and the most promising compound showed a MIC90 of 4 μM against M. tuberculosis cell growth. In silico docking experiments explained the species selectivity observed for this compound series.
Article
Chemistry, Multidisciplinary
Andrew J. Taylor, Andrew Docker, Paul D. Beer
Summary: A heteroditopic receptor with halogen bonding (XB) and hydrogen bonding was used to investigate the cooperative mechanisms of alkali metal halide ion-pair recognition. The study demonstrated the importance of allosteric pre-organization, electrostatics, and XB potency in enhancing halide anion binding affinity.
CHEMISTRY-AN ASIAN JOURNAL
(2023)
Article
Biotechnology & Applied Microbiology
Qing-Qing Yang, Wai-Han Yu, Hong-Yu Wu, Chang-Quan Zhang, Samuel Sai-Ming Sun, Qiao-Quan Liu
Summary: Lysine is the main limiting essential amino acid in rice seeds, and through the construction of mutants, this study effectively increased the free lysine content in rice seeds, showing potential in improving the nutritional quality of rice and other cereal grains.
PLANT BIOTECHNOLOGY JOURNAL
(2021)
Article
Computer Science, Artificial Intelligence
Hao Tian, Xi Jiang, Peng Tao
Summary: Allostery plays a crucial role in regulating protein activity, and identifying allosteric sites is essential for drug development. The ensemble learning method presented in this study shows good performance in predicting allosteric sites, with 84.9% accuracy in the test set.
MACHINE LEARNING-SCIENCE AND TECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jiayi He, Ivan J. Dmochowski
Summary: This study investigated the molecular mechanisms of xenon (Xe) action in bacteriophage T4 lysozyme (T4L) using both experimental and computational methods. The results showed that Xe exerts allosteric inhibition on the protein by expanding a C-terminal hydrophobic cavity, resulting in conformational changes and enzyme inhibition. The study also highlighted the potential use of Xe flooding simulations to discover new binding pockets.