Article
Biochemistry & Molecular Biology
Matteo Masetti, Martina Bertazzo, Maurizio Recanatini, Stefano Ciurli, Francesco Musiani
Summary: The survival of pathogenic bacteria like Helicobacter pylori relies on the activity of nickel dependent enzyme urease. Nickel insertion into urease is mediated by a multimeric chaperone complex. Research suggests that nickel can be transported through a series of stations found along internal pathways.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2021)
Review
Neurosciences
Wenyan Han, Ryan D. Shepard, Wei Lu
Summary: The majority of fast inhibitory transmission in the brain is mediated by GABA acting on GABA(A) receptors, providing inhibitory balance to excitatory drive. Recent studies have revealed that transmembrane proteins interact with GABA(A)Rs and modulate their function and trafficking, offering new dimensions in studying GABA(A)Rs. Targeting these receptor associated membrane proteins may lead to the development of new GABA(A)R psychopharmacology.
TRENDS IN NEUROSCIENCES
(2021)
Editorial Material
Biochemistry & Molecular Biology
Silke Pudewell, Mohammad Reza Ahmadian
Summary: The RTK-RAS-MAPK axis is extensively studied and related to cancer and RASopathies. However, directly targeting this cascade is still insufficient due to issues like drug toxicity, resistance, and low efficacy. Significant progress has been made in understanding the spatiotemporal features of the axis's constituent members, with many of these modulators emerging as potential therapeutic targets.
Article
Biochemical Research Methods
Jingzhe Shang, Na Han, Ziyi Chen, Yousong Peng, Liang Li, Hangyu Zhou, Chengyang Ji, Jing Meng, Taijiao Jiang, Aiping Wu
Summary: Accessory proteins play crucial roles in coronavirus-host interactions. A standardized genome annotation tool, CoroAnnoter, was developed to study the composition, evolutionary patterns, and host interactions of accessory proteins in coronaviruses. Variations in the number of accessory proteins were observed among different coronaviruses, with SARS-CoV-2 and SARS-CoV having the most. Evolutionary analysis revealed conservation and diversity in the distribution of accessory proteins within and between different genera of coronaviruses. Additionally, comparison of virus-host interaction networks of SARS-CoV-2 and SARS-CoV accessory proteins showed shared antiviral signaling pathways and biological processes.
BRIEFINGS IN BIOINFORMATICS
(2021)
Review
Medicine, Research & Experimental
Milad Zandi, Maryam Shafaati, Davood Kalantar-Neyestanaki, Hossein Pourghadamyari, Mona Fani, Saber Soltani, Hassan Kaleji, Samaneh Abbasi
Summary: The accessory proteins of SARS-CoV-2 play significant roles in immune evasion and viral pathogenesis, making them potential targets for drug development. The IFN-I and IFN-III responses are essential for clearing the infection. Several SARS-CoV-2 accessory proteins, such as ORF3a, ORF7a, and ORF7b, inhibit the host's IFN-beta response.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Jie Cheng, Peng Zhao, Lin Zhu, Fang Zhu, Zhiqiang Tian, Zhongjian Shen, Xiaoming Liu, Xiaoxia Liu
Summary: In this study, the neuropeptide Corazonin (Crz) and its receptor were characterized in Grapholita molesta, and their role in regulating copulation duration and fertility in males was investigated. Knockdown of Crz or its receptor led to prolonged copulation duration and decreased fertility in males without affecting sperm production. The knockdown also resulted in significantly diminished levels of accessory gland proteins and downregulation of genes involved in serine-type endopeptidase activity in the accessory gland. Furthermore, disruption of sperm activation in the spermatophore of females mated with knockdown males was observed. These findings provide new insights into the functions of Crz signaling in Lepidopteran insects.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Entomology
Li-Juan Wu, Fan Li, Yue Song, Zhan-Feng Zhang, Yong-Liang Fan, Tong-Xian Liu
Summary: The study identified and analyzed male accessory gland proteins (ACPs) in the diamondback moth, Plutella xylostella. A comparison with ACPs in other insect species revealed some new ACPs. This research provides valuable information for understanding the reproductive physiology of P. xylostella.
Article
Multidisciplinary Sciences
Zhengrong Xu, Lingna Guo, Xiaoyun Qian, Chenjie Yu, Shengju Li, Chengwen Zhu, Xiaofeng Ma, Hui Li, Guangjie Zhu, Han Zhou, Wenxuan Dai, Qian Li, Xia Gao
Summary: In this study, we identified two entry tunnels in the olfactory receptor TAAR9 and described the residues that form these tunnels. We also confirmed the function of these tunnels through site-directed mutagenesis, challenging the existing views regarding the number of entry tunnels and demonstrating their possible role in odorant recognition.
SCIENTIFIC REPORTS
(2022)
Article
Computer Science, Information Systems
Ben Wu, Wei Liu, Peixin Shi, Xiangyang Xu, Yingjing Liu
Summary: This study investigates the response of existing tunnels to the excavation of over-crossing tunnels. The in-situ monitoring results show that the vertical displacement of the existing tunnels is mainly uplift, and its development exhibits obvious phase characteristics. The superposition method is used to describe the uplift section characteristics of the existing tunnels.
INTERNATIONAL JOURNAL OF DISTRIBUTED SENSOR NETWORKS
(2022)
Review
Microbiology
Chongyang Wang, Ting Wang, Liuyuan Duan, Hui Chen, Ruochen Hu, Xiangwei Wang, Yanqing Jia, Zhili Chu, Haijin Liu, Xinglong Wang, Shuxia Zhang, Sa Xiao, Juan Wang, Ruyi Dang, Zengqi Yang
Summary: Paramyxoviruses have developed multiple strategies to evade host antiviral innate immunity, with accessory proteins playing a key role in antagonizing type I interferon production and other antiviral innate immune responses. The mechanisms by which these accessory proteins target adaptors in the antiviral innate immune signaling pathway to facilitate virus replication vary among viruses. Additionally, cellular responses involved in viral replication will be briefly summarized.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Virology
Puxian Fang, Liurong Fang, Huichang Zhang, Sijin Xia, Shaobo Xiao
Summary: Coronavirus accessory proteins, though dispensable for replication in vitro, play crucial roles in regulating immunity, proliferation, and pathogenicity. Their function in virus infection and pathogenesis, particularly in interaction with host cells, is of significant interest.
Review
Immunology
Natalia Redondo, Sara Zaldivar-Lopez, Juan J. Garrido, Maria Montoya
Summary: This article summarizes the current knowledge of SARS-CoV-2 accessory proteins, highlighting their roles during infection and impact on the host immune response.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Anna Spackova, Ondrej Vavra, Tomas Racek, Vaclav Bazgier, David Sehnal, Jiri Damborsky, Radka Svobodova, David Bednar, Karel Berka
Summary: ChannelsDB 2.0 is an updated database that provides structural information about the position, geometry, and physicochemical properties of protein channels and pores. It incorporates data calculated by CAVER and MOLE tools, as well as additional information from AlphaFill database, resulting in significantly expanded channel annotations. The database stores information such as geometrical features and physico-chemical properties based on channel-lining amino acids, and is interlinked with UniProt mutation annotation data. ChannelsDB 2.0 serves as an important resource for in-depth analysis of the role of biomacromolecular tunnels and pores.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Multidisciplinary Sciences
Fusheng Si, Shuai Song, Ruisong Yu, Zhen Li, Wenqiang Wei, Chao Wu
Summary: In this review, the current knowledge of the ORF3 protein in PEDV is summarized, with focus on its unique biological features and potential role in viral behavior and pathogenesis. Gaps in understanding are identified, and intriguing questions are proposed to stimulate further studies and collaboration among virologists worldwide.
Article
Microbiology
Sijin Xia, Puxian Fang, Ting Pan, Wenwen Xiao, Huichang Zhang, Xuerui Zhu, Shaobo Xiao, Liurong Fang
Summary: The study revealed that PDCoV NS7a possesses viroporin-like activity, enhancing membrane permeability, forming homooligomers, with essential amino acid residues 69FLR71.
VETERINARY MICROBIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Tobias Muhlethaler, Lampros Milanos, Jose Antonio Ortega, Thorsten B. Blum, Dario Gioia, Bibhas Roy, Andrea E. Prota, Andrea Cavalli, Michel O. Steinmetz
Summary: This study developed an antitubulin small molecule, Todalam, through two rounds of chemical synthesis based on a crystallographic fragment screen. Todalam binds to a novel tubulin site, disrupts microtubule networks, induces cell death, and synergizes with vinblastine. It destabilizes microtubules by inhibiting the conformational switch in alpha-tubulin and sequestering tubulin dimers. This work demonstrates the importance of using tubulin-binding fragments for innovative antitubulin drug and chemical probe discovery campaigns.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Luisa Iommarini, Ivana Kurelac, Beatrice Cavina, Agnese Fornasa, Daniele Traversa, Maria Iorio, Manuela Sollazzo, Monica De Luise, Eleonora Lama, Hamid Razi Nasiri, Anna Ghelli, Francesco Musiani, Giuseppe Gasparre, Anna Maria Porcelli
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2022)
Article
Biochemistry & Molecular Biology
Jacopo Carbone, Alessia Ghidini, Antonio Romano, Luca Gentilucci, Francesco Musiani
Summary: PacDOCK is a free and user-friendly web server that helps analyze molecular docking results and improve the efficiency of computer-aided drug design.
Article
Chemistry, Physical
S. Decherchi, G. Ciccotti, A. Cavalli
Summary: We address the problem of estimating free energy from the perspectives of regularization and Bayes estimation theory. By utilizing prior knowledge of the free energy, we reformulate the Bennett acceptance ratio method and present a numerical algorithm to solve it. Additionally, we provide a closed formula to estimate confidence in the prior. Finally, the derived estimators are tested on a toy model.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Riccardo Aguti, Mattia Bernetti, Stefano Bosio, Sergio Decherchi, Andrea Cavalli
Summary: Allostery is a crucial feature of biomolecular systems, impacting their functioning through intricate interplays between residues and protein structures. Computational approaches for correlation estimation provide insights into these complexes but can lead to different conclusions and outcomes. This article compares three computational methods on pharmaceutical targets, revealing consensus in some aspects but also highlighting the importance of different notions in identifying specific pockets and communications.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
S. Decherchi, A. Cavalli
Summary: Optimal transport theory is a growing field of mathematics with numerous applications. In this work, we utilize optimal transport for computational free energy estimation and demonstrate its effectiveness in optimizing barriers of alchemical transformations through analytical and simulation-based approaches.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Review
Chemistry, Multidisciplinary
Francesco Di Palma, Carlo Abate, Sergio Decherchi, Andrea Cavalli
Summary: Drug discovery is challenging and prone to failure. Computational methods for identifying ligandable pockets are recommended due to their inexpensiveness and speed, especially when supported by machine learning methodologies. However, the outcome of these methods depends on the input data and the modeling assumptions made.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2023)
Article
Biochemical Research Methods
Luca Mazzei, Rebecca Greene-Cramer, Khushboo Bafna, Aleksandar Jovanovic, Anna De Falco, Thomas B. Acton, Catherine Ann Royer, Stefano Ciurli, Gaetano T. Montelione
Summary: This article presents a protocol for producing 3CLpro protease from SARS-CoV-2 in Escherichia coli, including steps for purification and isotope-enriched samples suitable for NMR studies. The article also describes methods for characterizing 3CLpro using mass spectrometry, X-ray crystallography, heteronuclear NMR, and an enzyme assay. For complete details, please refer to the cited paper.
Article
Medicine, Research & Experimental
Maurizio Recanatini, Luca Menestrina
Summary: Diseases can be considered as emergent properties of living systems stemming from their complexity, and the use of network models has been introduced to describe drug-disease systems and make predictions about them. This article reviews recent examples of network science tools and predictive models in addressing drug-disease systems.
WIRES MECHANISMS OF DISEASE
(2023)
Article
Chemistry, Medicinal
Sarmistha Majumdar, Francesco Di Palma, Francesca Spyrakis, Sergio Decherchi, Andrea Cavalli
Summary: Tyrosine kinases play critical roles in cellular machinery, and dysregulation of their active or inactive forms is associated with diseases like cancer. This study aimed to comprehensively understand the flexibility-activity relationships of tyrosine kinases, focusing on pockets and fluctuations. By conducting molecular dynamics simulations, pocket and residue fluctuation analysis, and using a complementary machine learning approach, we studied 43 different tyrosine kinases. We found that the inactive forms often exhibit increased flexibility, particularly at the DFG motif level. Notably, using long simulations and a decision tree, we identified a semi-quantitative fluctuation threshold of the DGF+3 residue, beyond which the kinase is more likely to be in the inactive form.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Flavio Costa, Riccardo Ocello, Carlo Guardiani, Alberto Giacomello, Matteo Masetti
Summary: hERG is a voltage-gated potassium channel involved in heart contraction and its defects are associated with Long QT Syndrome type 2. The drug RPR260243 has the potential to treat LQTS2 by enhancing the opening of the channel. However, the molecular mechanism of its action is not well understood.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Irene Brusa, Elvira Sondo, Emanuela Pesce, Valeria Tomati, Dario Gioia, Federico Falchi, Beatrice Balboni, Jose Antonio Ortega Martinez, Marina Veronesi, Elisa Romeo, Natasha Margaroli, Maurizio Recanatini, Stefania Girotto, Nicoletta Pedemonte, Marinella Roberti, Andrea Cavalli
Summary: A new RNF5 inhibitor, called 1,2,4-thiadiazol-5-ylidene, has been discovered in this study. It selectively corrects the folding defect of CFTR protein in CF patients and has no toxic side effects. This finding provides evidence for the pursuit of novel treatment strategies for CF.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Giorgia Frumenzio, Balasubramanian Chandramouli, Neva Besker, Alessandro Grottesi, Carmine Talarico, Francesco Frigerio, Andrew Emerson, Francesco Musiani
Summary: Thanks to recent research on SARS-CoV-2, we now understand how the virus infects host cells through its spike protein and the role of TMPRSS2 protein in this process. This study used molecular dynamics simulations to investigate the conformational changes of TMPRSS2 and found that an inhibitor stabilizes the catalytic site and induces rearrangements in the protein's extracellular domain, creating a new cavity near the ligand binding pocket. These findings suggest a potential new drug target for improving TMPRSS2 recognition.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Barbara Zambelli, Priyanka Basak, Heidi Hu, Mario Piccioli, Francesco Musiani, Valquiria Broll, Lionel Imbert, Jerome Boisbouvier, Michael J. Maroney, Stefano Ciurli
Summary: The maturation pathway for urease involves the protein UreE as a metallochaperone, and accessory proteins HypA and HypB are also required in H. pylori. A protein complex forms between HypA and the UreE(2) dimer, mediated by conserved motifs and extensive protein contacts. This complex contains a high-affinity Ni(II)-binding site and a six-coordinate, high-spin Ni(II) site with ligands from both component proteins.
Article
Chemistry, Multidisciplinary
Jayoh A. Hernandez, Paul S. Micus, Sean Alec Lois Sunga, Luca Mazzei, Stefano Ciurli, Gabriele Meloni
Summary: Essential trace metals play crucial roles in the survival and virulence of bacterial pathogens. Helicobacter pylori requires nickel for colonization and persistence in the stomach, and NixA is an essential nickel transporter in this process. This study characterizes the selectivity and electrogenic nature of NixA-mediated nickel transport.