Article
Biochemistry & Molecular Biology
Kevin M. Knight, Soumadwip Ghosh, Sharon L. Campbell, Tyler J. Lefevre, Reid H. J. Olsen, Alan Smrcka, Natalie H. Valentin, Guowei Yin, Nagarajan Vaidehi, Henrik G. Dohlman
Summary: Proteins are crucial in signal transduction and pharmacology, with G proteins playing a central role. Research has shown that a conserved network of amino acids dictates the release of G protein subunits, providing insights into the molecular basis of G protein activation.
Article
Multidisciplinary Sciences
Janik B. Hedderich, Margherita Persechino, Katharina Becker, Franziska M. Heydenreich, Torben Gutermuth, Michel Bouvier, Moritz Buenemann, Peter Kolb
Summary: Researchers computationally describe alternative allosteric pockets in G-protein-coupled receptors, identifying nine previously untargeted sites for synthetic ligands. They further investigate the potential of modulating receptor function through ligand binding to these sites.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Amanda E. Wakefield, David Bajusz, Dima Kozakov, Gyoergy M. Keseru, Sandor Vajda
Summary: Despite the limited number of GPCR structures cocrystallized with allosteric inhibitors, protein mapping has revealed the presence of druggable sites at the same locations in a large variety of GPCRs. These sites cluster at nine distinct locations and can be specifically targeted for allosteric modulation across GPCRs. The FTMap server facilitates protein mapping and is freely available for academic and governmental use.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Multidisciplinary
Antonella Ciancetta, Amandeep Kaur Gill, Tianyi Ding, Dmitry S. Karlov, George Chalhoub, Peter J. McCormick, Irina G. Tikhonova
Summary: This study developed a probe confined dynamic mapping protocol to predict allosteric sites on GPCRs, demonstrating the advantage of specific probes derived from GPCR allosteric ligand structures over commonly used cosolvents in allosteric site mapping. The protocol was successfully validated retrospectively on selected receptors and prospectively on the D-2 dopamine receptor, confirming the prediction through subsequent mutagenesis. It provides a fast and efficient prediction of key amino acid residues surrounding allosteric sites in membrane proteins, aiding in the design of allosteric modulators based on protein structure.
ACS CENTRAL SCIENCE
(2021)
Article
Multidisciplinary Sciences
Joshua A. Lees, Joao M. Dias, Francis Rajamohan, Jean-Philippe Fortin, Rebecca O'Connor, Jimmy X. Kong, Emily A. G. Hughes, Ethan L. Fisher, Jamison B. Tuttle, Gabrielle Lovett, Bethany L. Kormos, Rayomand J. Unwalla, Lei Zhang, Anne-Marie Dechert Schmitt, Dahui Zhou, Michael Moran, Kimberly A. Stevens, Kimberly F. Fennell, Alison E. Varghese, Andrew Maxwell, Emmaline E. Cote, Yuan Zhang, Seungil Han
Summary: This study reports the structures of GPR61 in its active and inactive states, as well as the discovery of a small molecule inverse agonist that competes with G protein. These findings provide important structural insights and a tool compound for further exploration of GPR61 function and modulation.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Hui-Yuan Zhang, Ze-Hao Hou, Yan Zhang, Zhi-Yong Li, Jun Chen, Yong-Bin Zhou, Ming Chen, Jin-Dong Fu, You-Zhi Ma, Hui Zhang, Zhao-Shi Xu
Summary: The soybean GmEF8 gene plays a positive role in regulating drought and heat stresses in Arabidopsis and soybean, and its overexpression enhances the plants' tolerance to these stresses.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Plant Sciences
Runmin Che, Yuerong Liu, Shengqi Yan, Chao Yang, Yubo Sun, Changhai Liu, Fengwang Ma
Summary: This study reveals that overexpression of the heat-sensitive elongation factor Tu (MdEF-Tu) in apple positively regulates thermotolerance by maintaining photosynthetic capacity and chloroplast integrity. The chaperone heat shock protein (MdHsp70) is found to interact with MdEF-Tu, preventing the accumulation of aggregates and enhancing transgenic plant's thermotolerance.
Article
Cell Biology
Jakob Mitgau, Julius Franke, Camilla Schinner, Gabriele Stephan, Sandra Berndt, Dimitris G. Placantonakis, Hermann Kalwa, Volker Spindler, Caroline Wilde, Ines Liebscher
Summary: This study provides information on the structural requirements and forces needed for ECM-mediated activation of the GPR126 receptor. The N terminus of GPR126 acts as an allosteric module that can fine-tune receptor activation in a context-specific manner.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Microbiology
Neeraja Marathe, Ha An Nguyen, John N. Alumasa, Alexandra B. Kuzmishin Nagy, Michael Vazquez, Christine M. Dunham, Kenneth C. Keiler
Summary: This study reports a small molecule inhibitor called KKL-55 that specifically targets the interaction between EF-Tu and tmRNA, inhibiting bacterial translation without affecting normal translation. This discovery provides a potential avenue for developing new antibiotics to treat drug-resistant infections.
Article
Multidisciplinary Sciences
Tina Perica, Christopher J. P. Mathy, Jiewei Xu, Gwendolyn M. Jang, Yang Zhang, Robyn Kaake, Noah Ollikainen, Hannes Braberg, Danielle L. Swaney, David G. Lambright, Mark J. S. Kelly, Nevan J. Krogan, Tanja Kortemme
Summary: This study reveals that the functional specificity of the small GTPase switch protein Gsp1 in Saccharomyces cerevisiae is linked to the differential sensitivity of biological processes to different kinetics of the Gsp1 switch cycle. By making targeted point mutations to individual protein interaction interfaces of Gsp1 and conducting quantitative genetic and physical interaction mapping, it is shown that interface mutations allosterically tune the GTPase cycle kinetics, rather than grouping by targeted interfaces. These findings suggest a model in which protein partner binding or post-translational modifications may act as allosteric regulators of GTPase switching and may have implications for disease mutations targeting central molecular switches.
Article
Plant Sciences
Khem Raj Ghusinga, Timothy C. Elston, Alan M. Jones
Summary: G-proteins are molecular switches that transmit extracellular signals to intracellular targets. In plants, the role of nucleotide exchange in this process is less critical, but under dynamic conditions, the loss of RGS results in a strong phenotype.
Article
Chemistry, Medicinal
Jigang Fan, Yaqin Liu, Ren Kong, Duan Ni, Zhengtian Yu, Shaoyong Lu, Jian Zhang
Summary: Allostery is a fundamental mechanism in signal transmission, with allosteric drugs offering unique pharmacological advantages. The experimental approaches for developing allosteric modulators are traditionally serendipitous. The reversed allosteric communication theory provides a feasible tool for unbiased detection of allosteric sites.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Natsumi Maruta, Yuri Trusov, Alan M. Jones, Jose R. Botella
Summary: Plant G proteins consist of canonical G alpha subunits and unconventional XLG subunits, interacting with G beta gamma dimers and RGS protein, and participating in development, stress responses, and immunity. Despite the overall similarity between plant and animal G alpha subunits, they convey signals differently.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Masahiro Matsuo, Kazuyuki Seo, Akiyuki Taruno, Yasutaka Mizoro, Yoshiaki Yamaguchi, Masao Doi, Rhyuta Nakao, Hiroshi Kori, Takaya Abe, Harunori Ohmori, Keiko Tominaga, Hitoshi Okamura
Summary: This study reveals the role of Gem protein in regulating calcium signaling in the circadian clock. Gem inhibits VDCCs to attenuate light-induced calcium signaling. Deficiency of Gem leads to increased phase-shift magnitude in locomotor activity rhythms under light exposure, which can be normalized by blocking VDCCs.
Review
Endocrinology & Metabolism
Siyuan Shen, Chang Zhao, Chao Wu, Suyue Sun, Ziyan Li, Wei Yan, Zhenhua Shao
Summary: GPCRs, as the largest family of transmembrane proteins, regulate various physiological processes. However, their complicated signal transduction pathways and difficulties in drug development have presented challenges. By identifying new ligands that bind to allosteric sites, safer drugs for treating various diseases can be designed.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Chemistry, Physical
Aaron S. Rury, Christine Ferry, Jonathan Ryan Hunt, Myungjin Lee, Dibyendu Mondal, Sean M. O. O'Connell, Ethan N. H. Phan, Zaili Peng, Pavel Pokhilko, Daniel Sylvinson, Yingsheng Zhou, Chi H. Mak
JOURNAL OF PHYSICAL CHEMISTRY C
(2016)
Article
Chemistry, Physical
Garima Jindal, Dibyendu Monda, Arieh Warshel
JOURNAL OF PHYSICAL CHEMISTRY B
(2017)
Article
Chemistry, Physical
Dibyendu Mondal, Jacob Florian, Arieh Warshel
JOURNAL OF PHYSICAL CHEMISTRY B
(2019)
Article
Chemistry, Physical
Dibyendu Mondal, Vesselin Kolev, Arieh Warshel
Article
Chemistry, Physical
Arjun Saha, Gabriel Oanca, Dibyendu Mondal, Arieh Warshel
JOURNAL OF PHYSICAL CHEMISTRY B
(2020)
Article
Multidisciplinary Sciences
Dibyendu Mondal, Vesselin Kolev, Arieh Warshel
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
Dibyendu Mondal, Arieh Warshel
Article
Chemistry, Multidisciplinary
Chen Bai, Junlin Wang, Dibyendu Mondal, Yang Du, Richard D. Ye, Arieh Warshel
Summary: GPCRs are important integral membrane receptor proteins essential for various signaling processes. Although crystal structures of GPCRs have been solved, the detailed mechanism of their activation process remains poorly understood.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Li Na Zhao, Dibyendu Mondal, Weifeng Li, Yuguang Mu, Philipp Kaldis
Summary: Research has shown that changes in pH can affect the catalytic activity of lignin-degrading enzymes, highlighting the determinant role of protonation state of active site residues in the hydrolysis of PDC.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2022)
Article
Chemistry, Multidisciplinary
Dibyendu Mondal, Tumpa Sadhukhan, Iqbal A. Latif, Sambhu N. Datta
JOURNAL OF CHEMICAL SCIENCES
(2015)