Article
Biochemistry & Molecular Biology
Nan Zhou, Xiaoqing Yuan, Qingsong Du, Zhiyu Zhang, Xiaolei Shi, Jinku Bao, Yuping Ning, Li Peng
Summary: FerrDb V2 is the successor of the first ferroptosis database, providing a wealth of information on ferroptosis regulators and their associations with diseases. Compared to the previous version, FerrDb V2 includes a significantly larger number of curated articles and ferroptosis regulators. The integration of external gene-related data enables in-depth analysis.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Atanas Kamburov, Ralf Herwig
Summary: Molecular interactions play a crucial role in biological function. ConsensusPathDB serves as a meta-database combining various types of interactions, allowing researchers to evaluate and retrieve complex molecular neighborhoods. The integrated protein-protein interaction network forms the basis for propagation methods and provides additional functionality and improved stability.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Jyrki P. Kukkonen
Summary: Recent data indicates cooperative effects between identical orthosteric binding sites in a G-protein-coupled receptor dimer. A mathematical model was created to test this concept, showing that even a neutral receptor ligand can allosterically affect agonist binding through the orthosteric binding site.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Raudah Lazim, Donghyuk Suh, Jai Woo Lee, Thi Ngoc Lan Vu, Sanghee Yoon, Sun Choi
Summary: The presence of GPCR dimers has sparked research into their importance in disease pathogenesis and drug design, uncovering new signaling pathways and potential therapeutic targets. The increasing influence of computational methods in research is providing new avenues for understanding the functions and interactions of GPCRs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Mark Montgomery, Stefano Rendine, Christoph T. Zimmer, Jan Elias, Jurgen Schaetzer, Thomas Pitterna, Fides Benfatti, Marisa Skaljac, Aurelien Bigot
Summary: The development of novel and safe insecticides is crucial for protecting crops and animal and human health. In this study, the crystal structures of several insecticides were revealed, leading to the discovery of new pharmacophores with a related mode of action.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
David Rosenkranz, Hans Zischler, Daniel Gebert
Summary: The PIWI/piRNA system plays diverse roles in animals, including protection of germline cells, gene regulation, antiviral defense, and somatic transposon repression. piRNA clusters serve as the major source of piRNAs in almost all metazoan species, with highly divergent genomic loci influencing piRNA populations in different taxonomic groups.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Plant Sciences
Valerie Cognat, Gael Pawlak, David Pflieger, Laurence Drouard
Summary: PlantRNA is a comprehensive database of tRNA gene sequences retrieved from various photosynthetic organisms, covering the entire phylogenetic tree. The database includes a large number of accurately annotated tRNA genes and provides detailed biological information.
Article
Cell Biology
Simon Lind, Dagny Olofsson Hoffmann, Huamei Forsman, Claes Dahlgren
Summary: By studying the effects of the FFA2R ligand GLPG0974 on neutrophil activation, we discovered that GLPG0974 acts as an antagonist, agonist, and positive modulator of FFA2R. It affects NADPH-oxidase activity and alters receptor-downstream signaling induced by the co-agonistic PAMs.
CELLULAR SIGNALLING
(2022)
Article
Chemistry, Physical
Wei Chen, Guanxing Chen, Lu Zhao, Calvin Yu-Chian Chen
Summary: The study introduced a novel method using graph neural networks and BiLSTM to predict drug-target interactions, combined with BERT and BFS for efficient training, resulting in a high-performing model that can screen potential drugs and offer biological insights.
JOURNAL OF PHYSICAL CHEMISTRY A
(2021)
Article
Biochemical Research Methods
Xiaodi Yang, Xianyi Lian, Chen Fu, Stefan Wuchty, Shiping Yang, Ziding Zhang
Summary: The study introduces a database called HVIDB that provides comprehensive annotated data on human-virus protein-protein interactions and integrates online PPI prediction tools. Users can easily access reliable information on various human virus PPIs and conduct in-depth analysis through this database.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Annamaria Sandomenico, Alessia Ruggiero, Emanuela Iaccarino, Angela Oliver, Flavia Squeglia, Miguel Moreira, Luciana Esposito, Menotti Ruvo, Rita Berisio
Summary: CD59 is an abundant protein in humans that protects cells from damage by inhibiting the complement system. It inhibits the assembly of the Membrane Attack Complex (MAC) and is incorporated by pathogenic viruses like HIV-1 to escape complement-mediated virolysis. CD59 is also overexpressed in cancer cells to resist complement attack. In this study, bioinformatics and computational tools were used to identify CD59 interactions and design paratope-mimicking peptides that target CD59.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Stephen Price, Stephane Tombeur, Alexander Hudson, Nanda Kumar Sathiyamoorthy, Paul Smyth, Anjana Singh, Mara Peccianti, Elisa Baroncelli, Ahmed Essaghir, Ilaria Ferlenghi, Sanjay Kumar Phogat, Gurpreet Singh
Summary: Comparing protein structures is crucial for various biological problems, and TMQuery offers a continuously updated database with pre-computed TM-score values for every pair of proteins in the Protein Data Bank, allowing researchers to quickly access these values through a web interface.
Review
Biochemical Research Methods
Laura Pasquardini, Alessandra Maria Bossi
Summary: Protein molecular imprinting involves forming biomimetics with specific protein-recognition abilities through template-assisted synthesis, which has been successfully applied in separations, assays, sensors, and imaging. The process needs to ensure the preservation of the protein's three-dimensional structure, and imprinting only a portion of the protein can reduce costs and improve compatibility.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2021)
Letter
Biotechnology & Applied Microbiology
M. Michael Gromiha, Kannan Harini
Summary: Mei and colleagues introduced PNATDB, a thermodynamic database for protein-nucleic acid interactions with 12,635 experimentally determined parameters. They claimed that extracting data from existing databases is challenging. However, they did not discuss ProNAB, which contains over 20,000 experimental data points for binding affinities of protein-nucleic acid complexes and other information.
TRENDS IN BIOTECHNOLOGY
(2023)
Article
Microbiology
Heidy Elkhaligy, Christian A. Balbin, Jessica Siltberg-Liberles
Summary: Protein-protein interactions in eukaryotes are driven by short linear motifs (SLiMs). Conserved SLiMs can help identify functional SLiMs in eukaryotic protein families. However, the simplicity of eukaryotic SLiMs makes them appear by chance not only in eukaryotes but also in pathogenic bacteria and viruses. Additionally, functional eukaryotic SLiMs often exist in disordered regions. Pathogenic bacteria and viruses have less disorder in their proteomes compared to eukaryotes, but their proteins can mimic and disrupt eukaryotic SLiMs. Finding important SLiMs in pathogens is challenging but essential for understanding host-pathogen interactions. A comparative analysis of SLiMs across viruses, bacteria, and eukaryotes showed that viral SLiMs and certain motifs found in both viruses and eukaryotes have less disorder. The analysis of structural features of equivalent SLiMs from pathogens and eukaryotes revealed that some motifs are more structured in pathogens while others are more structured in eukaryotes, suggesting a varied mechanism of interaction between pathogens and their eukaryotic hosts.
Article
Biochemistry & Molecular Biology
Nicolas Bosc, Christophe Muller, Laurent Hoffer, David Lagorce, Stephane Bourg, Carine Derviaux, Marie-Edith Gourdel, Jean-Christophe Rain, Thomas W. Miller, Bruno O. Villoutreix, Maria Miteva, Pascal Bonnet, Xavier Morelli, Olivier Sperandio, Philippe Roche
ACS CHEMICAL BIOLOGY
(2020)
Article
Medicine, Research & Experimental
Laetitia Ganier, Xavier Morelli, Jean-Paul Borg
M S-MEDECINE SCIENCES
(2020)
Article
Oncology
Jeremy Ariey-Bonnet, Kendall Carrasco, Marion Le Grand, Laurent Hoffer, Stephane Betzi, Mikael Feracci, Philipp Tsvetkov, Francois Devred, Yves Collette, Xavier Morelli, Pedro Ballester, Eddy Pasquier
MOLECULAR ONCOLOGY
(2020)
Article
Cell Biology
R. Leblanc, R. Kashyap, K. Barral, A. L. Egea-Jimenez, D. Kovalskyy, M. Feracci, M. Garcia, C. Derviaux, S. Betzi, R. Ghossoub, M. Platonov, P. Roche, X. Morelli, L. Hoffer, Pascale Zimmermann
JOURNAL OF EXTRACELLULAR VESICLES
(2020)
Review
Cell Biology
Florent Colin, Kristine Schauer, Ali Hamiche, Pierre Martineau, Jean-Paul Borg, Jan Bednar, Giulia Bertolin, Luc Camoin, Yves Collette, Stephan Dimitrov, Isabelle Fournier, Vincent Hyenne, Marco A. Mendoza-Parra, Xavier Morelli, Philippe Ronde, Izabela Sumara, Marc Tramier, Patrick Schultz, Jacky G. Goetz
Summary: Cancer is a multi-step disease involving genetic, epigenetic, and environmental factors, as well as complex interactions between malignant and non-malignant cells in the tumour microenvironment. Deciphering the molecular complexes and cellular processes at play is crucial for effectively treating cancer and identifying new therapeutic targets.
BIOLOGY OF THE CELL
(2021)
Article
Biochemistry & Molecular Biology
Abdullah Aldehaiman, Afaque A. Momin, Audrey Restouin, Luyao Wang, Xiaoli Shi, Safia Aljedani, Sandrine Opi, Adrien Lugari, Umar F. Shahul Hameed, Luc Ponchon, Xavier Morelli, Mingdong Huang, Christian Dumas, Yves Collette, Stefan T. Arold
Summary: The Nef protein enhances viral pathogenicity by interacting with host cell proteins. Its polyvalency and binding selectivity enable it to disrupt host cell functions, particularly by tightly binding to Src family kinases' SH3 domains. Nef's flexible regions and core domain can allosterically influence ligand selection, promoting coherent protein ensembles. Only a small percentage of human proteins show Nef-like SH3 selectivity, mainly through canonical linear interactions.
BIOCHEMICAL JOURNAL
(2021)
Article
Chemistry, Medicinal
Florian Malard, Eric Jacquet, Naima Nhiri, Christina Sizun, Amelie Chabrier, Samir Messaoudi, Jerome Dejeu, Stephane Betzi, Xu Zhang, Aurelien Thureau, Ewen Lescop
Summary: TCTP protein is a pharmacological target in cancer, and its interactions with drugs such as sertraline and thioridazine have been explored using multiple techniques. The study revealed weaker drug binding compared to previous reports and found that phosphorylation at S46 does not enhance the interaction between TCTP and sertraline. Alternative modes of action for the drugs in tumor cells are discussed in light of these findings.
Article
Microbiology
Y. Cherrak, I. Filella-Merce, V. Schmidt, D. Byrne, V. Sgoluppi, R. Chaiaheloudjou, S. Betzi, X. Morelli, M. Nilges, R. Pellarin, E. Durand
Summary: The increasing drug-resistance of bacterial infections poses a threat to human health. Targeting the T6SS virulence factor as a potential strategy to combat pathogens, particularly antibiotic-resistant species, is a promising approach. The development of T6SS inhibitors could provide new therapeutic options to fight drug-resistant infections.
Article
Chemistry, Medicinal
Manon Garcia, Laurent Hoffer, Raphael Leblanc, Fatiha Benmansour, Mikael Feracci, Carine Derviaux, Antonio Luis Egea-Jimenez, Philippe Roche, Pascale Zimmermann, Xavier Morelli, Karine Barral
Summary: Syntenin stimulates exosome production and is implicated in cancer metastasis. Through fragment-based drug design, novel inhibitors targeting syntenin-syndecan interactions were developed. Optimization of a fragment led to the discovery of compounds that selectively affect syntenin-exosome release.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Laetitia Ganier, Stephane Betzi, Carine Derviaux, Philippe Roche, Charlotte Dessaux, Christophe Muller, Laurent Hoffer, Xavier Morelli, Jean-Paul Borg
Summary: PTK7 plays a role in the regulation of the Wnt/beta-catenin pathway and is overexpressed in colorectal cancer (CRC). Targeting the interaction between PTK7 and beta-catenin could be a potential therapeutic strategy for inhibiting cell growth dependent on the Wnt signaling pathway. In addition, inhibiting the kinase domain-dependent functions of PTK7 may also be of interest for further therapeutic development.
ACS CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Medicinal
Kendall Carrasco, Camille Montersino, Carine Derviaux, Magali Saez-Ayala, Laurent Hoffer, Audrey Restouin, Remy Castellano, Justine Casassa, Philippe Roche, Eddy Pasquier, Sebastien Combes, Xavier Morelli, Yves Collette, Stephane Betzi
Summary: A BDII-selective compound was discovered through screening the Fr-PPIChem chemical library, showing low activity in cell-based assays but the ability to modulate anti-leukemic activity in combination with various drugs in a cell- and context-dependent differential manner.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Laurent Hoffer, Manon Garcia, Raphael Leblanc, Mikael Feracci, Stephane Betzi, Khaoula Ben Yaala, Avais M. Daulat, Pascale Zimmermann, Philippe Roche, Karine Barral, Xavier Morelli
Summary: To address the challenge of early hit identification and optimization in drug discovery, we created a strategy called DOTS, which combines molecular dynamic simulations, computer-based library design with encoded medicinal chemistry reactions, constrained docking, and automated compound evaluation. We successfully applied the DOTS strategy to a challenging oncology target, syntenin, and created a best-in-class sub-micromolar small molecule inhibitor validated in cancer cell assays. The key to the success of our DOTS approach was the integration of protein conformational sampling during hit identification and synthetic feasibility ranking of the designed compounds during the optimization process. This approach can be widely used for other protein targets with known 3D structures to rapidly identify and optimize compounds as chemical probes and therapeutic candidates.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biophysics
Yu Wang, Zhipu Luo, Xavier Morelli, Peng Xu, Longguang Jiang, Xiaoli Shi, Mingdong Huang
Summary: In this study, the direct binding of lysophospholipids (lysoPLs), specifically LPC, to human serum albumin (HSA) was demonstrated using fluorescence quenching and optical interferometry assays. The crystal structure analysis revealed the binding sites of LPC on HSA and showed that HSA can still bind to LPC in the presence of myristate. These findings provide insights into the role of HSA as a carrier protein for lysoPLs in blood plasma and the structural basis of their binding mechanisms.
BIOPHYSICAL JOURNAL
(2023)