Article
Chemistry, Applied
O. N. Makshakova, E. R. Safarova, Y. F. Zuev
Summary: This study investigated the molecular interactions between RNase and polysaccharides, revealing the impact of polysaccharide side chains on protein structure in complexes. Computational simulations and spectroscopic analyses confirmed stable interactions, with potential implications for using rhamnogalacturonan I as a matrix material for protein delivery systems.
CARBOHYDRATE POLYMERS
(2021)
Article
Biochemistry & Molecular Biology
Eleni Chontzopoulou, Christina D. Papaemmanouil, Maria Chatziathanasiadou, Dimitrios Kolokouris, Sofia Kiriakidi, Athina Konstantinidi, Ioanna Gerogianni, Theodore Tselios, Ioannis K. Kostakis, Evangelia D. Chrysina, Dimitra Hadjipavlou-Litina, Demeter Tzeli, Andreas G. Tzakos, Thomas Mavromoustakos
Summary: The study indicates that aspartame could potentially inhibit LOX-1 and block its biological response, serving as a novel starting point for drug design against LOX enzyme. Various in silico and experimental studies were conducted to evaluate the potency of natural and artificial sweeteners in inhibiting the lipoxygenase enzyme, providing insight into their potential therapeutic applications.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Biochemistry & Molecular Biology
T. Reid Alderson, Lewis E. Kay
Summary: The article demonstrates the importance of nuclear magnetic resonance (NMR) spectroscopy in studying the dynamic structures of biomolecules, including its wide range of applications in revealing biomolecular motions, functional dynamics in large molecular machines, transient conformations implicated in disease onset, and weak interactions involved in liquid-liquid phase separation.
Article
Chemistry, Multidisciplinary
Xiaoqian Lin, Kaidong Lin, Shiqi He, Yue Zhou, Xiu Li, Xubo Lin
Summary: Plasmamembrane segregation into various nanoscale membrane domains is driven by distinct interactions between diverse lipids and proteins. Among them, liquid-ordered (L (o)) membrane domains are defined as lipid rafts and liquid-disordered (L (d)) ones as lipid non-rafts. Using model membrane systems, both intra-leaflet and inter-leaflet dynamics of these membrane domains are widely studied. Nevertheless, the biological impact of the latter, which is accompanied by membrane domain registration/anti-registration, is far from clear. Hence, in this work, we studied the biological relevance of the membrane domain anti-registration using both all-atom molecular dynamics (MD) simulations and confocal fluorescence microscopy. All-atom MD simulations suggested an intrinsic transmembrane potential for the case of the membrane anti-registration (L (o)/L (d)). Meanwhile, confocal fluorescence microscopy experiments of HeLa and 293T cell lines indicated that membrane cholesterol depletion could significantly alter the transmembrane potential of cells. Considering differences in the cholesterol content between L (o) and L (d) membrane domains, our confocal fluorescence microscopy experiments are consistent with our all-atom MD simulations. In short, membrane domain anti-registration induces local membrane asymmetry and, thus, an intrinsic transmembrane potential.
Article
Multidisciplinary Sciences
Yanan Zhao, Jiaojiao Hu, Shan-Shan Yang, Jing Zhong, Jianping Liu, Shuo Wang, Yuzhuo Jiao, Fang Jiang, Ruiyang Zhai, Bingnan Ren, Hua Cong, Yuwei Zhu, Fengtong Han, Jixian Zhang, Yue Xu, Zhiwei Huang, Shengnan Zhang, Fan Yang
Summary: In this study, the authors report the discovery of a redox switch for AcrIIC1, which regulates the protein's structure transition and inhibitory activity on Cas9. By replacing the key redox-sensitive amino acids, they generated a more stable and efficient variant, providing insights for the design of CRISPR-Cas systems.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Henning Windeck, Fabian Berger, Joachim Sauer
Summary: The location of Bronsted-acid sites at different crystallographic positions of zeolite catalysts influences their reactivity. By selecting the most stable conformers, it is found that the strength of internal H-bonds and the OH bond length vary substantially with the framework position. The experimental results support the previously debated assignments of H-bonded b-OH sites.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Jan H. Overbeck, Jennifer Vogele, Felix Nussbaumer, Elke Duchardt-Ferner, Christoph Kreutz, Jens Wohnert, Remco Sprangers
Summary: The synthetic neomycin-sensing riboswitch interacts with neomycin, ribostamycin, and paromomycin. However, only neomycin can efficiently repress translation initiation due to differences in ligand:riboswitch dynamics. Five complementary fluorine-based NMR methods were used to accurately quantify dynamics in the riboswitch complexes and identified four structurally different states. These findings highlight the potential of F-19 NMR methods in characterizing complex exchange processes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Oncology
Sreekumar Usha Devi Aiswarya, Gowda Vikas, Nair Hariprasad Haritha, Vijayasteltar Belsamma Liju, Anwar Shabna, Mundanattu Swetha, Tennyson Prakash Rayginia, Chenicheri Kizhakkeveettil Keerthana, Lekshmi Raghu Nath, Mullan Vellandy Reshma, Sankar Sundaram, Nikhil Ponnoor Anto, Ravi Shankar Lankalapalli, Ruby John Anto, Smitha Vadakkeveettil Bava
Summary: This study reports the anti-cancer potential of the ethnomedicinal plant C. epigaeus and its bioactive derivative Cu-B against melanoma. Cu-B exhibited cytotoxic effects on melanoma cells while being less toxic to normal skin fibroblasts. In vivo studies showed that Cu-B attenuated tumor growth without apparent toxicity. The anti-melanoma activity of Cu-B was associated with the inhibition of MAPK signaling. These findings suggest that C. epigaeus-derived Cu-B could be a potential source for developing potent and safe anti-cancer compounds.
FRONTIERS IN ONCOLOGY
(2022)
Article
Plant Sciences
Khong Trong Quan, InWha Park, Chung Sub Kim, Wesley Yoshida, Daneel Ferreira, Phuong Thien Thuong, Young Ho Kim, MinKyun Na, Joonseok Oh
Summary: A new benzo[g]isochromene with a conformationally mobile moiety was isolated from Rubia philippinensis. Advanced computational tools and compositional/molecular orbital analyses supported the configurational assignment. Compound 1 showed inhibitory effects on soluble epoxide hydrolase, which is linked to cardiovascular disorders.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Engineering, Chemical
Danuta Kruk, Elzbieta Masiewicz, Jaroslaw Budny, Karol Kolodziejski, Justyna Zulewska, Zbigniew Wieczorek
Summary: A broad range of H-1 spin-lattice relaxation studies have been conducted on different kinds of honey, with translation diffusion coefficients and rotational correlation times of water molecules in the sugar matrix determined. The translation dynamics of water molecules in honey is found to be three orders of magnitude slower than in bulk water, with systematic discrepancies observed compared to viscosity measurements. Activation energies of translational and rotational motion, as well as ratios between translational and rotational correlational times, have been determined and discussed in the context of supercooled liquids properties.
JOURNAL OF FOOD ENGINEERING
(2022)
Article
Biochemistry & Molecular Biology
Xiaolei Li, Xiao Su, Rui Liu, Yongsha Pan, Jiankai Fang, Lijuan Cao, Chao Feng, Qianwen Shang, Yongjing Chen, Changshun Shao, Yufang Shi
Summary: Pharmacological modulation of macrophage phenotype by HDAC inhibitors can reshape the tumor immune microenvironment, enhance anti-tumor immune responses, and improve the efficacy of immunotherapies in various tumors.
Article
Chemistry, Multidisciplinary
Rongfu Zhang, Timothy A. Cross, Xinhua Peng, Riqiang Fu
Summary: Understanding the dynamics and structure of water is crucial in biological systems. Directly probing the interfacial water in hydrated phospholipids is challenging, but a novel solid-state NMR technique was developed to successfully observe two distinct water species in the headgroup region of hydrated lipid bilayers. These findings provide an opportunity to study water dynamics on a millisecond or slower timescale in biomacromolecules.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Marzieh Dehghan Shasaltaneh, Elmira Naghdi, Zahra Moosavi-Nejad
Summary: This study investigates the interactions between RNase A and cCMP through molecular docking and molecular dynamics simulation. The results indicate that cCMP-RNase A complexes are stabilized through hydrophobic interaction, hydrogen bonding, and π-π stacking interaction. The enzyme-ligand docking study shows three phases of binding modes, and experimental methods confirm the activation and inhibition of substrate at different concentrations of cCMP.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Alida Besch, William M. Marsiglia, Moosa Mohammadi, Yingkai Zhang, Nathaniel J. Traaseth
Summary: Many human cancers are treated with small molecule inhibitors that target the kinase domain of receptor tyrosine kinases. Long-term treatment often leads to drug resistance mutations at the gatekeeper residue, increasing the aggressiveness of the cancer. However, the mechanism of gain-of-function by gatekeeper mutations is poorly understood.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
Ken Maes, Anna Mondino, Juan Jose Lasarte, Xabier Agirre, Karin Vanderkerken, Felipe Prosper, Karine Breckpot
Summary: Cancer cells can evade the immune system through epigenetic alterations, but epigenetic modulating agents have the potential to restore immunological fitness and overcome peripheral tolerance to transformed cells. By acting on both cancer cells and immune cells, EMAs represent interesting strategies for combinatorial therapies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Ruben Hervas, Maria del Carmen Fernandez-Ramirez, Albert Galera-Prat, Mari Suzuki, Yoshitaka Nagai, Marta Bruix, Margarita Menendez, Douglas V. Laurents, Mariano Carrion-Vazquez
Summary: The divergent prion-like domains (PLDs) of CPEB proteins from different species retain the ability to form a generic amyloid-like fold through different assembly mechanisms, with structural differences at the beginning of their amyloid assembly pathways.
Article
Biochemistry & Molecular Biology
Andrea Fagagnini, Miguel Garavis, Irene Gomez-Pinto, Sabrina Fasoli, Giovanni Gotte, Douglas V. Laurents
Summary: Protein oligomerization is crucial for various physiological processes and diseases, with human Angiogenin (h-ANG) playing a significant role in this process. Mutations in h-ANG can affect the surrounding residues and active site residues differently. Additionally, there is ongoing debate regarding the structure adopted by RNA fragments after cleavage by h-ANG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Andres Manuel Vera, Albert Galera-Prat, Michal Wojciechowski, Bartosz Rozycki, Douglas Laurents, Mariano Carrion-Vazquez, Marek Cieplak, Philip Tinnefeld
Summary: Cellulose is a renewable and abundant organic molecule used for biofuel and chemical production. Cellulosomes, composed of multiple enzymes, display unmatched efficiency in degrading lignocellulosic substrates. By studying the cohesin-dockerin interaction, multiple binding modes and a prolyl isomerase-modulated allosteric control mechanism were discovered, providing a novel understanding of the structural plasticity and dynamics of cellulosomes.
Article
Biochemistry & Molecular Biology
David Pantoja-Uceda, Cristiana Stuani, Douglas V. Laurents, Ann E. McDermott, Emanuele Buratti, Miguel Mompean
Summary: TDP-43 can form various aggregate forms, with droplets potentially evolving into fibrils or remaining in droplet form, influenced by different factors. Research unexpectedly observed droplet formation in the absence of salts or RNAs, visual evidence of fibrillization at the droplet surface/solvent interface, highlighting the key role of Phe-Gly motifs in fibril core formation.
Article
Biochemistry & Molecular Biology
Miguel Mompean, Javier Oroz, Douglas Laurents
Summary: Biomolecular condensates are microdroplets inside cells that selectively concentrate molecules for various physiological functions but can also contribute to diseases. Weak, transient interactions between molecules drive the formation of these condensates, and different types of condensates use distinct attractive interactions.
Article
Biochemistry & Molecular Biology
Nadide Altincekic, Sophie Marianne Korn, Nusrat Shahin Qureshi, Marie Dujardin, Marti Ninot-Pedrosa, Rupert Abele, Marie Jose Abi Saad, Caterina Alfano, Fabio C. L. Almeida, Islam Alshamleh, Gisele Cardoso de Amorim, Thomas K. Anderson, Cristiane D. Anobom, Chelsea Anorma, Jasleen Kaur Bains, Adriaan Bax, Martin Blackledge, Julius Blechar, Anja Bockmann, Louis Brigandat, Anna Bula, Matthias Buetikofer, Aldo R. Camacho-Zarco, Teresa Carlomagno, Icaro Putinhon Caruso, Betul Ceylan, Apirat Chaikuad, Feixia Chu, Laura Cole, Marquise G. Crosby, Vanessa de Jesus, Karthikeyan Dhamotharan, Isabella C. Felli, Jan Ferner, Yanick Fleischmann, Marie-Laure Fogeron, Nikolaos K. Fourkiotis, Christin Fuks, Boris Fuertig, Angelo Gallo, Santosh L. Gande, Juan Atilio Gerez, Dhiman Ghosh, Francisco Gomes-Neto, Oksana Gorbatyuk, Serafima Guseva, Carolin Hacker, Sabine Haefner, Bing Hao, Bruno Hargittay, K. Henzler-Wildman, Jeffrey C. Hoch, Katharina F. Hohmann, Marie T. Hutchison, Kristaps Jaudzems, Katarina Jovic, Janina Kaderli, Gints Kalnins, Iveta Kanepe, Robert N. Kirchdoerfer, John Kirkpatrick, Stefan Knapp, Robin Krishnathas, Felicitas Kutz, Susanne zur Lage, Roderick Lambertz, Andras Lang, Douglas Laurents, Lauriane Lecoq, Verena Linhard, Frank Loehr, Anas Malki, Luiza Mamigonian Bessa, Rachel W. Martin, Tobias Matzel, Damien Maurin, Seth W. McNutt, Nathane Cunha Mebus-Antunes, Beat H. Meier, Nathalie Meiser, Miguel Mompean, Elisa Monaca, Roland Montserret, Laura Marino Perez, Celine Moser, Claudia Muhle-Goll, Thais Cristtina Neves-Martins, Xiamonin Ni, Brenna Norton-Baker, Roberta Pierattelli, Letizia Pontoriero, Yulia Pustovalova, Oliver Ohlenschlaeger, Julien Orts, Andrea T. Da Poian, Dennis J. Pyper, Christian Richter, Roland Riek, Chad M. Rienstra, Angus Robertson, Anderson S. Pinheiro, Raffaele Sabbatella, Nicola Salvi, Krishna Saxena, Linda Schulte, Marco Schiavina, Harald Schwalbe, Mara Silber, Marcius da Silva Almeida, Marc A. Sprague-Piercy, Georgios A. Spyroulias, Sridhar Sreeramulu, Jan-Niklas Tants, Kaspars Tars, Felix Torres, Sabrina Toews, Miguel A. Trevino, Sven Trucks, Aikaterini C. Tsika, Krisztina Varga, Ying Wang, Marco E. Weber, Julia E. Weigand, Christoph Wiedemann, Julia Wirmer-Bartoschek, Maria Alexandra Wirtz Martin, Johannes Zehnder, Martin Hengesbach, Andreas Schlundt
Summary: The international COVID19-NMR consortium aims to gather scientific expertise worldwide to provide new approaches for understanding the molecular components of SARS-CoV-2. By making viral proteins and RNAs available, the consortium accelerates research on the virus and provides protocols for large-scale production. The NMR investigations and resources disclosed through the consortium offer valuable insights and tools for further studies on SARS-CoV-2.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
M. Mompean, B. S. McAvan, S. S. Felix, M. A. Trevino, J. Oroz, R. Lopez-Sanchez, D. Pantoja-Uceda, E. J. Cabrita, A. J. Doig, D. V. Laurents
Summary: The study suggests that Gly-rich proteins may form polyproline II helices to stabilize biomolecular condensates.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Sabrina Fasoli, Ilaria Bettin, Riccardo Montioli, Andrea Fagagnini, Daniele Peterle, Douglas V. Laurents, Giovanni Gotte
Summary: Human Angiogenin (hANG) is a protein that promotes vessel formation and is associated with diseases like PD and ALS. Research shows that ANG can form enzymatically active dimers through three-dimensional domain swapping, which could be crucial in understanding its role in neurodegenerative pathologies in the future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biophysics
Miguel Mompean, Miguel A. Trevino, Douglas V. Laurents
Summary: Intrinsically disordered proteins (IDPs) are important in regulating physiological processes in eukaryotic cells, and viruses use their own IDPs to disrupt host defenses. The C-terminal region (CtR) of SARS-CoV-2 Nsp2 interacts with human proteins, making it a potential drug target. NMR spectroscopy can provide atomic level information on the structure and dynamics of Nsp2's CtR.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Review
Biochemistry & Molecular Biology
Douglas V. Laurents
Summary: The artificial intelligence program AlphaFold 2 accurately predicts the 3D structure of two thirds of the human proteome, but it cannot provide insights into protein folding, stability, dynamics, and the impact of post translational modifications, mutations, or ligand binding. This is complemented by NMR spectroscopy which provides information on protein folding, dynamics, biomolecular condensates, amyloids, and their modulation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Multidisciplinary Sciences
Pablo Gracia, David Polanco, Jorge Tarancon-Diez, Ilenia Serra, Maruan Bracci, Javier Oroz, Douglas Laurents, Ines Garcia, Nunilo Cremades
Summary: This study reports the liquid-liquid phase separation of alpha-synuclein with Tau protein and identifies key factors that lead to the formation of hetero-aggregates inside the liquid protein condensates.
NATURE COMMUNICATIONS
(2022)
Article
Biophysics
Miguel A. Trevino, Ruben Lopez-Sanchez, Maria Redondo Moya, David Pantoja-Uceda, Miguel Mompean, Douglas Laurents
Summary: The use of polyproline II (PPII) helices in protein design is currently limited by our understanding of their stability and folding. However, recent studies on the snow flea antifreeze protein (sfAFP) suggest that a low entropy state contributes to folding thermodynamics. Analysis of sfAFP using NMR spectroscopy reveals a similar conformational entropy in the denatured state compared to typical proteins, indicating the potential for designing new structures based on PPII helical bundles.
BIOPHYSICAL JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Maria del Carmen Fernandez-Ramirez, Kevin Kan-Shing Ng, Margarita Menendez, Douglas V. Laurents, Ruben Hervas, Mariano Carrion-Vazquez
Summary: Understanding the early stages of amyloid formation is crucial for developing effective therapeutic strategies. Although the mechanism of tau protein aggregation, a key feature of neurodegenerative diseases, is still unclear, this study used single-molecule force spectroscopy to investigate the conformational landscape of the monomeric tau repeat domain. The researchers discovered different conformational states influenced by mutations and the chemical environment, with pathological mutations and an amyloidogenic milieu favoring expanded conformations. The findings provide insight into the complex aggregation process of tau protein and its relevance to different tauopathies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Sara S. Felix, Douglas V. Laurents, Javier Oroz, Eurico J. Cabrita
Summary: This study investigates the effect of metabolites on full-length (FL) FUS liquid-liquid phase separation (LLPS) and explores the behavior of the folded domains. It is found that FL FUS LLPS is maximal at low concentrations of glucose and glutamate, moderate concentrations of NaCl, Zn2+, and Ca2+, and at the isoelectric pH. The FUS RNA recognition motif (RRM) and zinc-finger (ZnF) domains undergo cold denaturation, exposing buried nonpolar residues that can participate in LLPS-promoting hydrophobic interactions.
Article
Multidisciplinary Sciences
Jaime Carrasco, Rosa Anton, Alejandro Valbuena, David Pantoja-Uceda, Mayur Mukhi, Ruben Hervas, Douglas V. Laurents, Maria Gasset, Javier Oroz
Summary: In this study, the authors demonstrate that metamorphism in the post-translationally modified TDP-43 prion-like domain plays a crucial role in disease mechanisms. They emphasize the significance of post-translationally modified chains as targets for disease intervention.
NATURE COMMUNICATIONS
(2023)