Article
Chemistry, Multidisciplinary
Biyue Zhu, Jing Yang, Richard Van, Fan Yang, Yue Yu, Astra Yu, Kathleen Ran, Keyi Yin, Yingxia Liang, Xunuo Shen, Wei Yin, Se Hoon Choi, Ying Lu, Changning Wang, Yihan Shao, Liang Shi, Rudolph E. Tanzi, Can Zhang, Yan Cheng, Zhirong Zhang, Chongzhao Ran
Summary: This study unexpectedly discovered several small molecules that can modulate antibody-epitope interactions, providing new possibilities for drug discovery and therapeutic modulation of auto-antibodies. The researchers also developed a new label-free screening technology for ligand discovery, which has multiple applications in biotechnology and drug discovery.
Article
Chemistry, Medicinal
Chen Chen, Xue Li, Huajun Zhao, Meng Liu, Jintong Du, Jian Zhang, Xinying Yang, Xuben Hou, Hao Fang
Summary: The combined use of a DNA minor groove binder and a histone deacetylase (HDAC) inhibitor has shown a synergistic antiproliferation effect. A new series of benzimidazole-hydroxamate hybrids were designed and synthesized to target both DNA minor groove and HDAC. The most active compounds 9k and 9l not only exhibited improved HDAC inhibitory activities but also showed potent antiproliferation activities against tumor cells. Importantly, these compounds demonstrated good in vivo antitumor efficacies and reshaped the tumor immune microenvironment by promoting antigen presentation, activating T cells, and polarizing tumor-infiltrating macrophages with antitumor activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Aaron Teran, Giarita Ferraro, Paola Imbimbo, Ana E. Sanchez-pelaez, Daria Maria Monti, Santiago Herrero, Antonello Merlino
Summary: This study explores the interaction between paddlewheel diruthenium complexes and proteins, and finds that their selectivity towards proteins is determined by their charge and steric properties. The anticancer activity of diruthenium derivatives is correlated with the number of ligands, steric hindrance, and core electronic density.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Avigail Stokar-Avihail, Taya Fedorenko, Jens Hor, Jeremy Garb, Azita Leavitt, Adi Millman, Gabriela Shulman, Nicole Wojtania, Sarah Melamed, Gil Amitai, Rotem Sorek
Summary: In recent years, various defense systems against phages have been found in bacteria. However, the mechanism of how these systems sense phage infection remains unknown. To address this question, the researchers isolated 177 phage mutants that can evade 15 different defense systems. These mutants were found to have mutations in the gene sensed by the defense system, providing insights into the determinants of phage sensitivity. The study identifies specific determinants of different retron systems and reveals phage-encoded triggers for abortive infection systems, shedding light on how bacterial immune systems sense phage invaders.
Article
Biochemistry & Molecular Biology
Sudip Dhakal, Paul A. Ramsland, Benu Adhikari, Ian Macreadie
Summary: This study utilized yeast as model organisms to screen 11 natural bioactive compounds and found that the combination of baicalein and trans-chalcone was most effective in reducing A beta(42) levels and decreasing ROS in yeast cells expressing native A beta(42) without affecting cell growth. Further studies are recommended to explore the potential cytoprotective activity of this combination in humans and determine the optimal dosage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Christophe Mesangeau, Pascal Carato, Nicolas Renault, Mathilde Coevoet, Paul-Emmanuel Larchanche, Amelie Barczyk, Luc Buee, Nicolas Sergeant, Patricia Melnyk
Summary: This paragraph discusses the rationale and methods for selecting small drug compounds based on structure-activity relationships. It also describes the various screening parameters used to identify compounds with potential anti-Alzheimer activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Chenju Yi, Ket Yin Goh, Lik-Wei Wong, Ajeena Ramanujan, Kazuhiro Tanaka, Sreedharan Sajikumar, Carlos F. Ibanez
Summary: In this study, it was found that mice expressing signaling-deficient variants of the p75 neurotrophin receptor showed greater neuroprotection from AD neuropathology in an animal model of AD. These variants interact with amyloid precursor protein (APP) at the plasma membrane and regulate its internalization, affecting amyloidogenic processing and disease progression. This suggests that inhibitors targeting the p75(NTR) transmembrane domain may be an effective therapeutic strategy in AD.
Article
Neurosciences
Min Zhu, Longfei Jia, Jianping Jia
Summary: The study identified miR-96-5p as the upstream miRNA for ABCA1, and inhibition of miR-96-5p in AD models could reduce A beta(42)/A beta(40) ratios by upregulating the expression of ABCA1, indicating an important role of miR-96-5p in regulating A beta content.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Multidisciplinary Sciences
Qing Dong, Nicholas W. Gentry, Thomas McMahon, Maya Yamazaki, Lorena Benitez-Rivera, Tammy Wang, Li Gan, Louis Ptacek, Ying-Hui Fu
Summary: Studies have shown that mutations in FNSS genes can modulate the development of tau and amyloid pathology in AD, indicating their potential role in neurodegeneration.
Article
Multidisciplinary Sciences
Jennifer West, Sandeep Satapathy, Daniel R. Whiten, Megan Kelly, Nicholas J. Geraghty, Emma-Jayne Proctor, Pietro Sormanni, Michele Vendruscolo, Joel N. Buxbaum, Marie Ranson, Mark R. Wilson
Summary: Neuroserpin has the ability to inhibit amyloid formation by multiple proteins and protect against associated cytotoxicity. It shows unique chaperone selectivity for intermediates on the amyloid-forming pathway, but has poor ability to inhibit amorphous protein aggregation. A conserved 14-residue region containing an alpha helix is identified, which may be useful in designing anti-amyloid reagents in the future.
Article
Chemistry, Inorganic & Nuclear
Ya-Ting Chen, Shao-Nan Zhang, Zhen-Feng Wang, Qing-Min Wei, Shu-Hua Zhang
Summary: In this study, 13 transition metal complexes were synthesized and characterized. Two novel complexes exhibited strong cytotoxic activities against A549/DDP cancer cells, inducing apoptosis and autophagy via the mitochondria! dysfunction pathway. These complexes also showed pronounced and selective activity against A549/DDP xenografts in vivo.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Medicinal
You Wang, Feng Xu, Connie B. Nichols, Yuqian Shi, Homme W. Hellinga, J. Andrew Alspaugh, Mark D. Distefano, Lorena S. Beese
Summary: Infections caused by fungal pathogens pose a challenge due to limited options for treatment and emerging resistance. This study highlights the urgent need for next-generation antifungal drugs. The researchers have developed compounds that effectively inhibit farnesylation, an essential process for the infectivity of Cryptoccoccus neoformans, a lethal pathogenic fungus. These compounds demonstrate high-affinity binding and superior efficacy compared to commonly used antifungals.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Cell Biology
Mohammad Rafi Khezri, Mehdi Mohebalizadeh, Morteza Ghasemnejad-Berenji
Summary: Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide, characterized by neuronal and synaptic loss in the central nervous system. The major causes of neuronal death in AD include accumulation of extracellular amyloid beta (Aβ) and aggregated tau proteins. Targeting the process of Aβ production to reduce its deposition has emerged as a potential therapeutic option for AD management. This review focuses on ADAM10, a protein involved in the non-amyloidogenic pathway of amyloid precursor protein processing, and discusses its molecular properties, role in AD, and potential as a therapeutic target to slow down disease progression.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Pharmacology & Pharmacy
Atukuri Dorababu
Summary: Alzheimer's disease is a neurodegenerative disease with increasing morbidity and mortality worldwide, the complex etiology of which poses challenges for prevention and treatment. Research focusing on discovering efficient drugs for AD is essential, with heterocyclic compounds playing a crucial role in drug discovery.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Joerg Benz, Arne C. Rufer, Sylwia Huber, Andreas Ehler, Melanie Hug, Andreas Topp, Wolfgang Guba, Eva Carolina Hofmann, Ravi Jagasia, Rosa Maria Rodriguez Sarmiento
Summary: This study identified a new class of GCase activators with specific binding mode, which may enhance substrate metabolism in lysosomes and have potential therapeutic implications for Parkinson's disease and Gaucher's disease. The findings provide important insights for future drug discovery efforts in the field of GCase activation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Samantha Schrecke, Yun Zhu, Jacob W. McCabe, Mariah Bartz, Charles Packianathan, Minglei Zhao, Ming Zhou, David Russell, Arthur Laganowsky
Summary: The study shows that the two isoforms of K(2P)4.1 have distinct preferences for binding to lipids, including acyl chain length, position, and fatty acid linkage. Phosphatidic acid has the best activation effect on the channel.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Man Pan, Qingyun Zheng, Yuanyuan Yu, Huasong Ai, Yuan Xie, Xin Zeng, Chu Wang, Lei Liu, Minglei Zhao
Summary: The human AAA+protein p97 plays a crucial role in cellular protein homeostasis. The study reveals insights into the interaction between p97 and its co-factor Npl4, showing three distinct conformational states of Npl4 in complex with human p97, suggesting the essential role of seesaw motion in the unfolding activity of the p97 complex.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Peleg Ragonis-Bachar, Meytal Landau
Summary: The amyloid state of protein aggregation is associated with neurodegenerative and systemic diseases, but can also serve physiological roles in various organisms. Recent advancements in cryogenic electron microscopy have expanded the repertoire of high-resolution amyloid structures, allowing for better understanding of their pathogenic or functional roles.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Matevz Rumpret, Helen J. von Richthofen, Maarten van der Linden, Geertje H. A. Westerlaken, Cami Talavera Ormeno, Jos A. G. van Strijp, Meytal Landau, Huib Ovaa, Nina M. van Sorge, Linde Meyaard
Summary: The study reveals that PSMs from different species of Staphylococcus can activate SIRL-1, leading to antimicrobial responses. These PSMs and human LL-37 may represent a potential new class of natural ligands for SIRL-1.
Article
Biochemistry & Molecular Biology
Yuanyuan Yu, Qingyun Zheng, Satchal K. Erramilli, Man Pan, Seongjin Park, Yuan Xie, Jingxian Li, Jingyi Fei, Anthony A. Kossiakoff, Lei Liu, Minglei Zhao
Summary: Protein ubiquitination exhibits remarkable diversity in topology and function through the polymerization of ubiquitin via different linkages, and deciphering the cellular ubiquitin code is crucial for understanding cell physiology. The synthetic antigen-binding fragment sAB-K29 was identified as a tool that can specifically recognize K29-linked polyubiquitin, leading to insights into the involvement of K29-linked ubiquitination in cellular proteotoxic stress response and cell cycle regulation.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Michal Mayer, Yulia Matiuhin, Mickal Nawatha, Orly Tabachnikov, Inbar Fish, Nili Schutz, Hay Dvir, Meytal Landau
Summary: The bacterial tyrosine kinase BceF from Burkholderia cepacia is structurally characterized in this study and found to have unique variations compared to other BY-kinases, offering a potential for development of specific inhibitors targeting Burkholderia cepacia virulence.
Article
Biochemistry & Molecular Biology
Yizhaq Engelberg, Peleg Ragonis-Bachar, Meytal Landau
Summary: Human LL-37(17-29) is an antimicrobial peptide that forms stable supramolecular fibrils surrounding bacterial cells. The morphology of the fibrils and their antibacterial mechanism may be dependent on their interactions with specific bacteria.
Article
Genetics & Heredity
Aarthi Kuppannan, Yu-Yang Jiang, Wolfgang Maier, Chang Liu, Charles F. Lang, Chao-Yin Cheng, Mark C. Field, Minglei Zhao, Martin Zoltner, Aaron P. Turkewitz
Summary: This study explores the mechanisms underlying the regulated exocytosis of mucocysts in the ciliate Tetrahymena thermophila. The researchers identify a novel gene, MDL1, which is essential for the regulated exocytosis of mucocysts. They also discover a macromolecular complex associated with MDL1 that is involved in the docking and discharge of mucocysts. These findings contribute to our understanding of cellular biodiversity and may have implications for developing therapies against human parasites.
Article
Biochemistry & Molecular Biology
Peleg Ragonis-Bachar, Bader Rayan, Eilon Barnea, Yizhaq Engelberg, Alexander Upcher, Meytal Landau
Summary: Amyloid protein fibrils and antimicrobial peptides share similar properties and self-assembly can act as a mechanism to regulate antimicrobial peptides. Human amyloids may also play a role in host defense against pathogens. 14 fibril-forming antimicrobial peptides from living organisms were identified and shown to have cross-beta and cross-alpha amyloid properties. These peptides, mainly produced by amphibians and marine creatures, may provide stability and adherence properties in different environments.
Article
Chemistry, Applied
Alon Romano, Yizhaq Engelberg, Meytal Landau, Uri Lesmes
Summary: This study explores the fabrication of bovine alpha-lactalbumin (ALA) amyloid-like fibrils (AF) for gastro-intestinal delivery of capsaicin (CAP). Acidic incubation of ALA with CAP accelerates formation of ALA-AF and diminishes the levels of bioaccessible bioactive peptides. This work provides a new possible avenue for designing protein structures to entrap bioactive moieties.
FOOD HYDROCOLLOIDS
(2023)
Article
Multidisciplinary Sciences
Jixing Lyu, Chang Liu, Tianqi Zhang, Samantha Schrecke, Nicklaus P. Elam, Charles Packianathan, Georg K. A. Hochberg, David Russell, Minglei Zhao, Arthur Laganowsky
Summary: In this study, the authors characterized the structural basis and functional roles of the bacterial ABC transporter MsbA binding to copper and specific lipids using native mass spectrometry, X-ray crystallography, cryo-EM, and biochemical approaches.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Microbiology
Meytal Landau
Review
Biochemistry & Molecular Biology
Rinat Yona Indig, Meytal Landau
Summary: The review discusses the role of amyloids in diseases and the challenges of targeting human amyloids in therapy development. However, there is increasing interest in repurposing anti-amyloid compounds for antivirulence therapy due to the understanding of microbial amyloids as virulence factors. The review highlights the importance of amyloid inhibitors in clinical implications and insights into amyloid structure and function.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tong Wu, Chang Liu, Siyuan Zou, Ruitu Lyu, Bowei Yang, Hao Yan, Minglei Zhao, Weixin Tang
Summary: Researchers have developed a new gene editing technology called enAsCas12f, which is one-third the size of SpCas9 and has 11.3-fold higher activity than AsCas12f. enAsCas12f exhibits greater DNA cleavage activity in vitro and in human cells, achieving up to 69.8% insertions and deletions at user-specified genomic loci. The cryo-electron microscopy structure of the AsCas12f-sgRNA-DNA complex reveals dimerization-mediated substrate recognition and cleavage. Additionally, engineers have created a shorter sgRNA-v2 with comparable activity to the full-length sgRNA. Overall, this work enables more reliable and precise gene editing in mammalian cells.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Peleg Ragonis-Bachar, Gabriel Axel, Shahar Blau, Nir Ben-Tal, Rachel Kolodny, Meytal Landau
Summary: This study evaluated the structure predictions of antimicrobial amyloids using the AlphaFold2 ColabFold method, showing its effectiveness in predicting the structures of antimicrobial peptides.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)