Review
Biochemistry & Molecular Biology
Veronika Obsilova, Tomas Obsil
Summary: Signal transduction cascades efficiently transmit chemical and/or physical signals from the extracellular environment to intracellular compartments, thereby eliciting an appropriate cellular response. 14-3-3 proteins, as a family of highly conserved scaffolding molecules, play a crucial role in modulating the function of other proteins primarily through phosphorylation-dependent mechanisms. They participate in key cellular processes such as cell-cycle control, apoptosis, signal transduction, energy metabolism, and protein trafficking. However, our understanding of the molecular mechanisms by which 14-3-3 proteins regulate their binding partners remains insufficient, despite intensive research into their protein-protein interactions. This review article aims to provide an overview of recent structural studies of 14-3-3 protein complexes in order to further explore the regulatory mechanisms of these proteins.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biology
Mahesh Kondapuram, Benedikt Frieg, Sezin Yueksel, Tina Schwabe, Christian Sattler, Marco Lelle, Andrea Schweinitz, Ralf Schmauder, Klaus Benndorf, Holger Gohlke, Jana Kusch
Summary: In this study, the crucial role of residue K464 of the C-linker in stabilizing the closed state of the mHCN2 channel was demonstrated through mutagenesis, patch-clamp technique, confocal patch-clamp fluorometry, and molecular dynamics simulations. The K464E mutation disrupted the interactions between subunits, favoring a pre-activated state of the channel.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemical Research Methods
Alican Gulsevin, Jens Meiler
Summary: The AmphiScan protocol is a tool developed to predict the interaction of amphipathic helices with membranes, with features of fast, accurate, and highly customizable.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Michael J. Roy, Minglyanna G. Surudoi, Ashleigh Kropp, Jianmei Hou, Weiwen Dai, Joshua M. Hardy, Lung-Yu Liang, Thomas R. Cotton, Bernhard C. Lechtenberg, Toby A. Dite, Xiuquan Ma, Roger J. Daly, Onisha Patel, Isabelle S. Lucet
Summary: PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. The researchers elucidate the molecular details of key PEAK signaling interactions with the adapter proteins CrkII and Grb2 and the scaffold protein 14-3-3. They identify a conserved high affinity 14-3-3 motif on PEAK3 and demonstrate its role as a molecular switch to regulate CrkII binding and signaling via Grb2.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Pavel Pohl, Rohit Joshi, Olivia Petrvalska, Tomas Obsil, Veronika Obsilova
Summary: The study investigated the structural basis of Nedd4-2 regulation by 14-3-3 and identified phosphorylated Ser342 and Ser448 as key residues facilitating 14-3-3 binding. The Nedd4-2:14-3-3 complex induces a structural rearrangement of Nedd4-2 by inhibiting interactions between its structured domains.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Physical
Ainara Claveras Cabezudo, Christina Athanasiou, Alexandros Tsengenes, Rebecca C. Wade
Summary: Reducing the nonbonded interactions between protein and water enables protein encapsulation in phospholipid micelles and bilayers.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Public, Environmental & Occupational Health
Isabel Guadano Procesi, Azzurra Carnio, Federica Berrilli, Margherita Montalbano Di Filippo, Alessia Scarito, Cristina Amoruso, Marco Barni, Marco Ruffini, Giulia Barlozzari, Manuela Scarpulla, Claudio De Liberato
Summary: The study detected and analyzed the genetic characteristics of G. duodenalis in colony stray cats in central Italy, revealing a surprisingly high prevalence of 35.3% in cats, with all positive cats being infected with zoonotic assemblages/sub-assemblages. This suggests that stray cats may serve as a possible source of human giardiasis and emphasizes the importance of cat colonies in the study area in terms of public health.
ZOONOSES AND PUBLIC HEALTH
(2022)
Article
Chemistry, Physical
D. Kumar, M. K. Meena, K. Kumari, R. Kumar, I Bahadur, P. Jain, P. Singh
Summary: Researchers are seeking effective drugs to treat chikungunya viral infections by inhibiting nsp3 activity, but the temperature may affect the inhibition of nsp3 of CHIKV by CMPD104.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Biochemistry & Molecular Biology
Hetao Chen, Hang Zhang, Pu Chen, Song Xiang
Summary: This study elucidated the interaction mechanism between CRTCs and 14-3-3, as well as their crucial roles in nuclear translocation and activation of gene transcription. The discovery of a novel salt bridge structure expanded the understanding of this interaction.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biology
George L. Hamilton, Nabanita Saikia, Sujit Basak, Franceine S. Welcome, Fang Wu, Jakub Kubiak, Changcheng Zhang, Yan Hao, Claus A. M. Seidel, Feng Ding, Hugo Sanabria, Mark E. Bowen
Summary: PSD-95 is a scaffold protein that links postsynaptic receptors to presynaptic neurotransmitter release sites. The study combines discrete molecular dynamics and single molecule FRET to characterize the supertertiary structure of PSD-95. The results reveal the conformational changes of PDZ3 and its binding ability to neuroligin.
Article
Chemistry, Multidisciplinary
Ipsita Pani, Fidha K. M. Nazreen, Monika Sharma, Santanu Kumar Pal
Summary: The study explores interactions between mitochondrial cardiolipin and membrane-associated cytochrome c using aqueous LC dispersions, unveiling lipid-protein interactions that drive reorientation at the LC droplet interface. This insight is fundamental for designing functional interfaces for a spectrum of interfacial applications.
Article
Biochemistry & Molecular Biology
Zoe Jelic Matosevic, Katarina Radman, Jolene Loubser, Ivo Crnolatac, Ivo Piantanida, Ignacy Cukrowski, Ivana Lescic Asler, Branimir Bertosa
Summary: The transcription factor MntR regulates Mn2+ ion homeostasis by binding to Mn2+ ions and enhancing its DNA-binding affinity. The binding of Mn2+ ions reduces the structural dynamics of MntR protein and shifts the conformation towards DNA binding. Additionally, Mn2+ binding also changes the helical structure and stability of MntR protein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Elisa Barroeta-Echegaray, Rocio Fonseca-Linan, Raul Arguello-Garcia, Rafael Rodriguez-Munoz, Rosa Maria Bermudez-Cruz, Porfirio Nava, M. Guadalupe Ortega-Pierres
Summary: Enolase produced by G. duodenalis initiates proteolysis of extracellular matrix components through plasminogen activation, affecting interactions between trophozoites and epithelial cells. These findings suggest that Giardia enolase acts as a virulence factor by inducing necroptotic-like cell processes mediated by TNF-alpha and AIF activities.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Physics, Multidisciplinary
Dominik Schildknecht, Thomson Matt
Summary: A new phenomenological model is introduced to explain self-organized transport phenomena in light-controlled active matter, highlighting the importance of center of mass conservation and the necessity of memory for sustained motility. The model generalizes to explain more complex interactions, providing a foundation for understanding and optimizing transport protocols in active matter devices.
NEW JOURNAL OF PHYSICS
(2021)
Article
Chemistry, Physical
Thomas S. Hofer
Summary: The extensive re-parametrisation of the flexible SPC-mTR water potential resulted in more suitable ensemble averages for the intramolecular geometry of ambient water, improved vibrational properties, and an adequate relative static permittivity. The optimization strategy followed successful three-point water models OPC3 and H2O-DC, utilizing overpolarized partial charges and modified intramolecular geometries. The improved structural, vibrational, and dielectric properties of the new SPC-mTR2 parametrisation are expected to provide superior performance in QM/MM-type simulations aimed at determining single-ion solvation free energies.
CHEMICAL PHYSICS LETTERS
(2021)
Article
Biotechnology & Applied Microbiology
Catherine Cazeaux, Marco Lalle, Loic Durand, Dominique Aubert, Loic Favennec, Jitender P. Dubey, Alain Geffard, Isabelle Villena, Stephanie La Carbona
Summary: The study characterized the performance criteria of real-time qPCR based-methods for detecting three protozoan parasites in mussel tissues through spiking experiments. Different processing methods significantly affected the detection results, with direct DNA recovery from concentrated hemolymph showing lower efficiency in detecting the protozoa.
Article
Biochemistry & Molecular Biology
Loretta Ferrera, Floriana Cappiello, Maria Rosa Loffredo, Elena Puglisi, Bruno Casciaro, Bruno Botta, Luis J. Galietta, Mattia Mori, Maria Luisa Mangoni
Summary: A study identified antimicrobial peptides (Esc peptides) with the ability to increase ion currents in CFTR and eradicate lung infections in cystic fibrosis patients, providing a new pharmacological approach for addressing CF lung disease.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mattia Mori, Claudiu T. Supuran
Summary: Acipimox is an effective inhibitor of carbonic anhydrase activity, interacting with metal ions and amino acid residues. This research is important for the design of more effective antiobesity drugs.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Francesca Picarazzi, Fabrizio Manetti, Valeria Marigo, Mattia Mori
Summary: The study investigated rhodopsin mutations at the P347 site within the C-terminal VAPA-COOH motif and found structural differences between the wild-type and mutant rhodopsin, offering insight into the pathogenic mechanisms of these mutations. This could potentially aid in the development of new therapeutic strategies for retinitis pigmentosa.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
Article
Infectious Diseases
Bruno Casciaro, Francesca Ghirga, Floriana Cappiello, Valeria Vergine, Maria Rosa Loffredo, Silvia Cammarone, Elena Puglisi, Carola Tortora, Deborah Quaglio, Mattia Mori, Bruno Botta, Maria Luisa Mangoni
Summary: In this study, a cheminformatics approach was used to cluster a library of natural products and their derivatives, leading to the identification of a novel antimicrobial compound, ferruginin A. The activity of ferruginin A against Gram-positive bacteria was found to be the most potent, and it showed better therapeutic index compared to two analogues.
Article
Chemistry, Medicinal
Giulia Siciliano, Veronica Di Paolo, Dante Rotili, Rossella Migale, Francesca Pedini, Marialuisa Casella, Serena Camerini, Daniele Dalzoppo, Rob Henderson, Tonnie Huijs, Koen J. Dechering, Antonello Mai, Anna Maria Caccuri, Marco Lalle, Luigi Quintieri, Pietro Alano
Summary: This work investigates the activity of NBDHEX and its carboxylic acid metabolite on the human malaria parasite Plasmodium falciparum. NBDHEX shows strong activity against all blood stages of the parasite, with a higher potency against the gametocytes. Covalent modifications of gametocyte proteins are found to be associated with the antiparasitic effect of NBDHEX. Both NBDHEX and its metabolite have limited cytotoxicity in vitro, making them potential starting points for the development of new drugs to block malaria transmission.
Article
Chemistry, Medicinal
Elizabeth A. Lopes, Raquel Mestre, Diana Fontinha, Jenny Legac, Jinxin Pei, Margarida Sanches-Vaz, Mattia Mori, Adele M. Lehane, Philip J. Rosenthal, Miguel Prudencio, Maria M. M. Santos
Summary: Malaria remains a prevalent infectious disease in developing countries. The emergence of resistance to current treatments necessitates the discovery of new effective drugs. A study reports the identification of a new scaffold with dual-stage antiplasmodial activity, highlighting the potential of new compounds as antimalarial agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Food Science & Technology
Rachel M. Chalmers, Frank Katzer, Stephanie La Carbona, Marco Lalle, Romy Razakandrainibe, Lucy J. Robertson, Guy Robinson, Barbara Soba, Tamirat Temesgen, Anne Mayer-Scholl
Summary: Protozoan parasites have become a significant concern for public health and the food industry, particularly in relation to fresh produce and berries. Current detection methods, such as microscopy, lack standardized protocols and validation data, hindering efforts to understand and report parasite occurrences accurately. The development of guidance for artificial contamination studies and the potential for molecular detection offer promising avenues for improving method consistency and food safety.
Article
Oncology
Tomasz Kowalczyk, Anna Merecz-Sadowska, Patricia Rijo, Mattia Mori, Sophia Hatziantoniou, Karol Gorski, Janusz Szemraj, Janusz Piekarski, Tomasz Sliwinski, Michal Bijak, Przemyslaw Sitarek
Summary: The Solanaceae family is important in agriculture and economy, containing valuable active secondary metabolites with biological and medical properties. This review focuses on the assessment of the anticancer properties of Solanaceae extracts and compounds, along with their synergistic effects with chemotherapeutic agents and nanoparticles. It also explores the potential molecular mechanisms in various cancer models. The study highlights the need for new alternative anticancer agents and the untapped potential of many Solanaceae plants.
Article
Microbiology
Nadia Maria Lopez Urena, Umer Chaudhry, Rafael Calero Bernal, Santiago Cano Alsua, Davide Messina, Francisco Evangelista, Martha Betson, Marco Lalle, Pikka Jokelainen, Luis Miguel Ortega Mora, Gema Alvarez Garcia
Summary: This study conducted a systematic review and found that Toxoplasma gondii oocysts were present in various matrices worldwide. The detection rates and sample heterogeneity were influenced by multiple factors. Harmonized detection methods are needed to obtain reliable and comparable results.
Article
Chemistry, Medicinal
Theo Battista, Stefano Federico, Simone Brogi, Luca Pozzetti, Tuhina Khan, Stefania Butini, Anna Ramunno, Eleonora Fiorentino, Stefania Orsini, Trentina Di Muccio, Annarita Fiorillo, Cecile Exertier, Daniel Di Risola, Andrea Ilari, Giuseppe Campiani, Gianni Colotti, Sandra Gemma
Summary: Leishmania spp. is a significant public health issue, and developing better therapeutic drugs is urgently needed. This study optimized a novel class of Leishmania inhibitors through various approaches and identified potent and selective compounds that could be used for treating leishmaniasis and related diseases.
ACS INFECTIOUS DISEASES
(2022)
Article
Microbiology
Mattia Mori, Deborah Quaglio, Andrea Calcaterra, Francesca Ghirga, Leonardo Sorrentino, Silvia Cammarone, Matteo Fracella, Alessandra D'Auria, Federica Frasca, Elena Criscuolo, Nicola Clementi, Nicasio Mancini, Bruno Botta, Guido Antonelli, Alessandra Pierangeli, Carolina Scagnolari
Summary: Flavonoids, such as baicalein, have been shown to inhibit the key enzyme 3CLpro of SARS-CoV-2 and exhibit antiviral activity against multiple coronaviruses.
Review
Chemistry, Medicinal
Elizabeth A. Lopes, Maria M. M. Santos, Mattia Mori
Summary: This article summarizes the recent patents on antimalarial small molecules and vaccines, highlighting the progress made in designing new drugs and their efficacy in animal models.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Biochemistry & Molecular Biology
Chiara Platella, Francesca Ghirga, Domenica Musumeci, Deborah Quaglio, Pasquale Zizza, Sara Iachettini, Carmen D'Angelo, Annamaria Biroccio, Bruno Botta, Mattia Mori, Daniela Montesarchio
Summary: In this study, five natural compounds were investigated as analogs of promising G-quadruplex-targeting ligands to identify highly effective and selective anticancer candidates. Among them, Dicentrine was found to be the most effective ligand for telomeric and oncogenic G-quadruplexes, showing good selectivity. In-depth studies demonstrated that Dicentrine thermally stabilizes G-quadruplexes without affecting the control duplex, with higher affinity for G-quadruplex structures. Molecular dynamics simulations indicated that Dicentrine preferentially binds the G-quadruplex groove or the outer G-tetrad. Biological assays confirmed that Dicentrine promotes potent and selective anticancer activity by inducing cell cycle arrest through apoptosis, targeting G-quadruplex structures at telomeres.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Mattia Mori, Francesca Ghirga, Beatrice Amato, Luca Secco, Deborah Quaglio, Isabella Romeo, Marta Gambirasi, Alberta Bergamo, Sonia Covaceuszach, Riccardo Sgarra, Bruno Botta, Guidalberto Manfioletti
Summary: HMGA proteins play important roles in regulating transcription, RNA processing, DNA repair, and chromatin remodeling. Through virtual screening and laboratory experiments, we identified natural compounds, including Sorocein C, that can compete with HMGA proteins for DNA binding and exhibit cytotoxic effects on cancer cells.