Cascade Bio的动态

???? Exciting news from the world of enzymatic chemistry! ?? Our latest paper titled "Intramolecular Coupling and Nucleobase Transfer – How Cytochrome P450 Enzymes GymBx Establish Their Chemoselectivity" has just been published! Cyclodipeptides are vital secondary metabolites with diverse pharmacological impacts ranging from antibiotics to potential Alzheimer's treatments. In our study, we delve into the intricate mechanisms behind the biosynthesis of these compounds. Our research sheds light on a newly discovered class of P450 enzymes, found in the biosynthetic pathway of guatyromycines. These enzymes exhibit a remarkable dual functionality, catalyzing both intramolecular C-C bond formation and a nucleobase transfer reaction, a unique trait among CDP-modifying P450 enzymes. By elucidating the crystal structures of these enzymes, we uncover crucial insights into those reactions. Our findings pinpoint key residues crucial for substrate recognition and highlight how enzymatic bifunctionality can be modified. Intriguingly, through mutagenesis, we successfully engineered a variant that dramatically alters the chemoselectivity of the reaction. This breakthrough paves the way for future protein engineering endeavors aimed at synthesizing novel CDP-nucleobase adducts with tailored pharmacological properties. This research represents a significant step forward in understanding the intricate biochemistry underlying secondary metabolite biosynthesis. We're excited about the potential implications of our findings and look forward to further exploration in this fascinating field! Read more: https://lnkd.in/eq2HmgUv #Biochemistry #StructureBasedProteinDesign #Research #Science #Chemistry #ProteinEngineering

??Thrilled to share some very exciting news! I am very excited to share that my first first-author research publication has been officially published in ?????????????? ?????????? ????????????????. In this paper, titled "Structure-based discovery of first inhibitors targeting the helicase activity of human PIF1", we share the joined efforts of medicinal chemists, biochemists, structural biologists and bio-informaticians that have resulted in a first series of compounds inhibiting the helicase and DNA-binding activities of human #PIF1, through crystallographic fragment screening. This project was the major focus of my PhD work at EDELRIS and Université Grenoble Alpes, and it wouldn't have been possible without the collaborative effort of all the incredible co-authors and colleagues: Cyril Sanders, Saba Dehghani-Tafti, Francesca Romana Scommegna, Iris helfrich, Sara Egea Rodríguez, Jose Brandao-Neto, Fred Antson, and Ben Bax. I am also particularly thankful to my mentors Vincent Rodeschini, Jean-Francois Poisson and Didier Roche for their support and help throughout this journey. Lastly, I would like to extend my gratitude to the #MSCA AntiHelix Project for funding this work and for the additional help in shaping this work. I hope our findings will contribute to the field as a whole and drive forward the development of new human PIF1 #inhibitors. Find the full article following this link: https://lnkd.in/egTDMXQf #DrugDiscovery #MedicinalChemistry #Crystallography #BioChemistry #Research

??????????Science Corner?????? The attached document discusses the complex chemistry of snake venom and its vast potential for medicinal use. Snake venom, composed primarily of proteins and peptides, varies significantly among species, making it a challenging yet promising source for drug development. This review examines the chemical composition of venom from over 200 snake species, focusing on the structure and activity of key toxins, including their impact on the nervous and cardiovascular systems. The diverse bioactive compounds in venom offer numerous opportunities for creating new therapeutic drugs, despite the challenges posed by venom variability. It highlights recent advances in the study of snake venom, including the identification of protein families that dominate venom composition in medically important snakes, such as those from the Elapidae and Viperidae families. These toxins have been shown to have potential therapeutic applications, ranging from neurotoxicity to myotoxicity and haemotoxicity. The authors emphasize the importance of understanding venom's molecular structure and reactivity to unlock its full medicinal potential, proposing strategies for transforming venom toxins into a broad array of new drugs. This research underscores the dual nature of snake venom as both a deadly poison and a source of life-saving medications. #science #venom #snakes #fascinating

Welcome to Wednesday Words, where each Wednesday morning I will give you a definition of one word used in biotechnology or biopharma! Metabolites are small molecules produced by metabolic processes in living organisms, including cells, tissues, and microorganisms. Metabolites play essential roles in cellular functions, energy production, and biochemical pathways, serving as building blocks, energy sources, and signaling molecules. Examples of metabolites include amino acids, sugars, lipids, nucleic acids, and organic acids, among others. Metabolite profiling and analysis are important tools in metabolomics research, providing insights into metabolic pathways, disease mechanisms, and biomarker discovery. If you want to learn more, check out: #wednesdaywords #biotechnology #biopharma

???I am thrilled to announce the publication of our latest research in Journal of Proteomics! Our study, titled "In-gel protein digestion using acidic methanol produces a highly selective methylation of glutamic acid residues," explores the strikingly specific methylation of glutamic acid during in-gel protein digestion, a method commonly used in proteomics studies. Our results have significant implications for unbiased post-translational modifications (PTMs) analyses using mass-tolerant open search methods and pave the way for more precise and accurate proteomic studies. Check out the full article here: https://lnkd.in/dc4Ps84H https://lnkd.in/dznKUVxt This study was the result of a large collaborative effort between our team at Hospital Universitario de la Princesa and the CNIC - Spanish National Center for Cardiovascular Research / Centro Nac. Investigaciones Cardiovasc.’s Proteomics Lab. Congratulations to all authors for their hard work and dedication!????? Emilio Camafeita, Inma Jorge Cerrudo, Andrea L., Rafael Barrero Rodríguez, Cristina Devesa Arbiol, Clara Pertusa Vi?uales, Enrique Calvo, Francisco Sánchez Madrid, Jesús Vázquez, Noa Martín Cófreces #Proteomics #Research #PostTranslationalModifications #OpenSearch #MassSpectrometry

"The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles" by Professor Dr. Marc Ilies and graduate student Shibbir Ahmed Khan was identified as a "Highly Cited Paper of 2023" by?International Journal of Molecular Sciences. "We have also highlighted the role played by different PLA2s in key physiologic processes in the human body and in different pathologies, ranging from inflammation and cancer to Alzheimer’s disease, with the aim of providing an up-to-date overview of the impact of this class of enzymes in human health and diseases." Read more at?https://lnkd.in/ehtThXSN Temple University #templemade #research International Journal of Molecular Sciences MDPI #biotech #medicalresearch #pharmaceuticalsciences #pharma #pharmaceuticalindustry #drugresearch #molecularsciences

#PNGaseF – Precision in #GlycoproteinAnalysis PNGase F is a highly efficient enzyme used for the removal of N-linked glycans from glycoproteins. By cleaving the bond between asparagine and the glycan, it aids in the study of glycosylation patterns and facilitates protein characterization. This enzyme is critical in mass spectrometry and proteomic workflows where precise deglycosylation is necessary for the accurate identification and quantification of glycoproteins. #PNGaseF #GlycoproteinDeglycosylation #Proteomics #MassSpectrometry #Glycobiology #ProteinCharacterization #Biotechnology

β-Oxidation --- β-oxidation is a crucial process for the metabolism of fatty acids. Though discovered some time ago and published 120 years ago, this metabolic pathway continues to be a relevant topic for researchers. Key points: - In prokaryotic cells, β-oxidation occurs in the cytosol, while in eukaryotic cells, it takes place in the mitochondria. - Short-chain fatty acids can freely enter mitochondria, but long-chain fatty acids require carnitine transport to cross the mitochondrial membrane. - For very long-chain fatty acids (more than 22 carbons), β-oxidation happens exclusively in peroxisomes. We put together some publications about fatty acid oxidation: https://lnkd.in/g4R42W25 #BetaOxidation #FattyAcidMetabolism #LipidResearch #biochemistry #Metabolism #lipotype #research #lipid #lipidomics #LipidMetabolism #lipidome

Essential Amino Acids and Non essential amino acids. for more detail like share and follow. #essentialaminoacids#bio #biochemistry #acid #protein #nonessentialaminoacids #molecules #study#student #viral #post #university #gene https://lnkd.in/dQxP9hWW like,share and follow for more detail@just_biochemist

All articles in Frontiers in Bioscience-Elite（ISSN: 1945-0494）-- Volume 16, Issue 3, are now freely available to access, read and download: https://lnkd.in/g5qBbbrt #bioscience #CellBiology #MolecularBiology #MedEd #biochem #MedicalScience #biotechnology #microbiology #cellular