Article
Biochemistry & Molecular Biology
Jose L. Neira, Martina Palomino-Schatzlein, Estefania Hurtado-Gomez, Maria G. Ortore, Alberto Falco
Summary: The study focused on the design of a specific fragment of the HPr protein, HPr48, which was shown to be disordered. Despite being only 48 residues long, HPr48 was capable of binding to other proteins and aiding in antimicrobial activity of antibiotics.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Multidisciplinary Sciences
George H. Tzertzinis, Mehul Ganatra, Cristian Ruse, Christopher Taron, Bryce Causey, Liang Wang, Ira Schildkraut
Summary: We report the discovery of a novel adenosine deaminase-related growth factor (ADGF) that specifically deaminates adenosine 5' monophosphate (AMP) rather than adenosine. ADGFs are secreted deaminases that regulate extracellular adenosine concentration by converting it to inosine. The AMP deaminase studied in this research was first identified and characterized from the snail Helix pomatia in 1983. Through sequence comparison and protein expression, it was determined that this AMP deaminase is a member of the ADGF family despite its preference for AMP over adenosine.
Article
Biochemical Research Methods
Richard A. Stein, Hassane S. Mchaourab
Summary: This study presents a general approach to drive Alphafold2 to model alternate protein conformations through manipulation of the multiple sequence alignment. The applicability of this approach is demonstrated through the investigation of membrane proteins, expanding the potential uses of Alphafold2.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Entomology
Johanna Rivas, Annabelle Fuentes, Annick Maria, Benjamin Bergerot, David Siaussat, David Renault
Summary: Environmental plastic pollution has increased in recent decades and has significant impacts on economies, human, and biodiversity health. Chemical additives in plastics, such as bisphenol A (BPA) and Di(2-ethylhexyl)phthalate (DEHP), can disrupt the endocrine system in animals, affecting physiological processes, reproduction, development, and behavior. Our study reveals that exposure to BPA and DEHP leads to increased oxidative stress.
JOURNAL OF INSECT PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shaokun Chen, Weiyi Lai, Yanan Li, Yan Liu, Jie Jiang, Xiangjun Li, Guibin Jiang, Hailin Wang
Summary: Intracellular decay of N-6-methyladenine (m6A)-containing RNA does not generate free 6mdA species or lead to misincorporation of DNA 6mdA in most tested mammalian cell lines, revealing a sanitation mechanism that prevents 6mdA misincorporation.
Review
Biochemistry & Molecular Biology
Rajasree Kalagiri, Tony Hunter
Summary: Histidine phosphorylation is a significant post-translational modification, with both 1- and 3-phosphohistidine isomers known. While pHis is commonly used as an enzyme intermediate in all organisms, its role in signal transduction is observed in prokaryotes, lower eukaryotes, and plants. Recent advancements in phosphoproteomic techniques and antibody development have accelerated our understanding of histidine phosphorylation, particularly in higher eukaryotes which is still a growing area of study.
BIOCHEMICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Jian Chang, Chengxin Zhang, Huaqiang Cheng, Yan-Wen Tan
Summary: Protein engineering using rational design by bioinformatics can enhance thermostability of proteins without time-consuming experimental screenings. Utilizing a primary-sequence-based algorithm can help identify amino acid sites related to thermostability, leading to the construction of mutants with improved enzymatic activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Justina Sileikyt, Sunil Sundalam, Larry L. David, Michael S. Cohen
Summary: Nicotinamide adenine dinucleotide (NAD(+)) is a multifunctional molecule with important functions in redox metabolism and as a substrate for post-translational modification enzymes. Recent discoveries of noncanonical NAD-binding proteins suggest a larger NAD interactome than previously thought. Newly designed chemical tools, 2- and 6-ad-BAD, have been shown to efficiently profile NAD-binding proteins.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Iain C. Clark, Bruk Mensa, Christopher J. Ochs, Nathan W. Schmidt, Marco Mravic, Francisco J. Quintana, William F. DeGrado, Adam R. Abate
Summary: Using a hybrid valve- and droplet-based microfluidic system, a combinatorial DNA library encoding an engineered histidine kinase based on bacterial CpxA was successfully constructed. Surprising results were found, such as the different effects on catalytic activity caused by the combinations of the S helix and TM domain. It was concluded that the intervening HAMP domain passively transmits signals and shapes the signaling response depending on subtle changes in neighboring domains, leading to a richness in functional outputs as HKs vary in response to changing evolutionary pressures.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Alessio Romerio, Nicole Gotri, Ana Rita Franco, Valentina Artusa, Mohammed Monsoor Shaik, Samuel T. Pasco, Unai Atxabal, Alejandra Matamoros-Recio, Marina Minguez-Toral, Juan Diego Zalamea, Antonio Franconetti, Nicola G. A. Abrescia, Jesus Jimenez-Barbero, Juan Anguita, Sonsoles Martin-Santamaria, Francesco Peri
Summary: In this study, a new series of small-molecule TLR4 agonists (the FP20 series) with increased chemical stability and a more efficient synthesis method were developed based on previously developed TLR4 ligands (the FP18 series). The FP20 series showed selective activity as TLR4 agonists, but with a different mechanism of action compared to the FP18 series. Computational studies suggested that the 3D shape of the FP20 series allows for binding to the MD-2 pocket. Additionally, FP20 displayed promising adjuvant activity in mouse vaccination experiments.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Meixiao Zhan, Yufeng Ding, Shanzhou Huang, Yuhang Liu, Jing Xiao, Hua Yu, Ligong Lu, Xiongjun Wang
Summary: By phosphorylating and stabilizing DHODH, sensitivity of liver cancer cells to Oxaliplatin is enhanced.
NATURE COMMUNICATIONS
(2023)
Article
Clinical Neurology
Jin Yang, Guibo Feng, Mingyue Chen, Shenglin Wang, Feng Tang, Jing Zhou, Nana Bao, Juming Yu, Guohui Jiang
Summary: This study investigated the effect of glucosamine on the behavior and electrophysiology of epileptic rats through the PI3K/Akt pathway. The results suggest that high doses of glucosamine may exacerbate epileptic seizures and facilitate the development of chronic epilepsy.
Article
Dentistry, Oral Surgery & Medicine
S. Wang, L. Long, X. Yang, Y. Qiu, T. Tao, X. Peng, Y. Li, A. Han, D. B. Senadheera, J. S. Downey, S. D. Goodman, X. Zhou, D. G. Cvitkovitch
Summary: VicRK system plays essential roles in regulating cell division, cell wall biosynthesis, and homeostasis in low-GC Gram-positive bacteria, as well as biofilm formation of Streptococcus mutans on the tooth surface. VicK, with both autokinase and phosphatase activities, regulates the bacterial response to environmental cues in S. mutans. The phosphatase activity of VicK is critical for maintaining optimal phosphorylation status of VicR, affecting cell growth, EPS synthesis, and bacterial agglutination in saliva.
JOURNAL OF DENTAL RESEARCH
(2021)
Article
Microbiology
Deborah Kang, Hyeong-In Ham, Seung-Hwan Lee, Yong-Joon Cho, Yeon-Ran Kim, Chang-Kyu Yoon, Yeong-Jae Seok
Summary: Research systematically analyzed the PTS components of F. prausnitzii in the human colon, identifying 16 genes encoding putative PTS components and determining the components responsible for phosphotransfer reactions and sugar-specific PTS components, providing insights into how F. prausnitzii outcompetes other bacterial species in the human intestine.
ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Alessio Romerio, Nicole Gotri, Ana Rita Franco, Valentina Artusa, Mohammed Monsoor Shaik, Samuel T. Pasco, Unai Atxabal, Alejandra Matamoros-Recio, Marina Minguez-Toral, Juan Diego Zalamea, Antonio Franconetti, Nicola G. A. Abrescia, Jesus Jimenez-Barbero, Juan Anguita, Sonsoles Martin-Santamaria, Francesco Peri
Summary: In this study, a panel of small-molecule TLR4 agonists (the FP20 series) was developed based on previously developed TLR4 ligands (the FP18 series). The FP20 series demonstrated improved chemical stability and a more efficient synthesis method. The molecules showed selective TLR4 agonist activity similar to FP18, but with a different mechanism of action involving MAPK and NLRP3-dependent inflammasome activation. Computational studies suggested that the 3D shape of the FP20 series contributes to their agonist binding properties within the MD-2 pocket. FP20 exhibited low toxicity and promising adjuvant activity in mouse vaccination experiments.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Matthew Jessulat, Shahreen Amin, Mohsen Hooshyar, Ramy Malty, Mohamed Taha Moutaoufik, Mara Zilocchi, Zoe Istace, Sadhna Phanse, Hiroyuki Aoki, Katayoun Omidi, Daniel Burnside, Bahram Samanfar, Khaled A. Aly, Ashkan Golshani, Mohan Babu
Summary: The deletion of the yeast PKA catalytic subunit Tpk1 reduces NHEJ efficiency by phosphorylating Nej1 to influence repair protein recruitment and DNA resection. In mammalian cells, the PRKACB homolog also plays a similar role in NHEJ repair by phosphorylating XLF.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Thiago Seraphim, Nardin Nano, Yiu Wing Sunny Cheung, Siripat Aluksanasuwan, Carolina Colleti, Yu-Qian Mao, Vaibhav Bhandari, Gavin Young, Larissa Holl, Sadhna Phanse, Yuliya Gordiyenko, Daniel R. Southworth, Carol Robinson, Visith Thongboonkerd, Lisandra M. Gava, Julio C. Borges, Mohan Babu, Leandro R. S. Barbosa, Carlos H. Ramos, Philipp Kukura, Walid A. Houry
Summary: The R2TP complex, formed by RUVBL1 and RUVBL2 ATPases, associates with PIH1D1 and RPAP3 proteins and plays a role in promoting the formation of macromolecular complexes. RPAP3 is identified as the central subunit of R2TP, linking PIH1D1 and RUVBL1/2. The study provides insights into the structure and function of the R2TP complex.
Review
Genetics & Heredity
Matineh Rahmatbakhsh, Alla Gagarinova, Mohan Babu
Summary: Microbial pathogens have evolved diverse strategies to manipulate host systems, causing diseases through changes in the host-pathogen proteome. Mass spectrometry-based proteomics approaches are utilized to study disease progression but present challenges in data analysis. The study reviews steps in temporal and spatial analysis, offering best practices for data preprocessing, statistical analysis, and biological information extraction. Guidance is provided for novices and established users, with future directions and data analysis codes available for testing.
FRONTIERS IN GENETICS
(2021)
Article
Multidisciplinary Sciences
Mara Zilocchi, Cheng Wang, Mohan Babu, Jingjing Li
Summary: The article discusses the qualitative and quantitative definitions of health, as well as understanding the molecular etiologies of diseases through a proteomic perspective. It highlights key proteomic approaches to identify pathogenic mutations and integrating omics data to define the borderline between health and disease.
Article
Biochemistry & Molecular Biology
Sang Hyun Lim, Jamie Snider, Liron Birimberg-Schwartz, Wan Ip, Joana C. Serralha, Hugo M. Botelho, Miqueias Lopes-Pacheco, Madalena C. Pinto, Mohamed Taha Moutaoufik, Mara Zilocchi, Onofrio Laselva, Mohsen Esmaeili, Max Kotlyar, Anna Lyakisheva, Priscilla Tang, Lucia Lopez Vazquez, Indira Akula, Farzaneh Aboualizadeh, Victoria Wong, Ingrid Grozavu, Teuta Opacak-Bernardi, Zhong Yao, Meg Mendoza, Mohan Babu, Igor Jurisica, Tanja Gonska, Christine E. Bear, Margarida D. Amaral, Igor Stagljar
Summary: Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a chloride and bicarbonate channel that plays a critical role in maintaining fluid homeostasis. Mutations in CFTR are associated with Cystic Fibrosis (CF), the most common lethal autosomal recessive disorder in Caucasians. This study used a high-throughput screening technique to map the protein-protein interactions of CFTR and identify potential drug targets for CF treatment. They discovered candidate proteins, such as FGL2, that may have significant effects on CFTR function in CF pathophysiology.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Virology
Subha Dahal, Ran Cheng, Peter K. Cheung, Terek Been, Ramy Malty, Melissa Geng, Sarah Manianis, Lulzim Shkreta, Shahrazad Jahanshahi, Johanne Toutant, Rose Chan, Sean Park, Mark A. Brockman, Mohan Babu, Samira Mubareka, Karen Mossman, Arinjay Banerjee, Scott Gray-Owen, Martha Brown, Walid A. Houry, Benoit Chabot, David Grierson, Alan Cochrane
Summary: In this study, the medicinal chemistry optimization of a known HIV-1 inhibitor led to the discovery of a new derivative, GPS491, which showed potent anti-HIV-1 activity with reduced toxicity. The study demonstrated that GPS491 not only blocked HIV-1 replication, but also inhibited the replication of adenovirus and multiple coronaviruses. Furthermore, GPS491 induced changes in viral RNA processing and altered the accumulation/phosphorylation/function of splicing regulatory SR proteins. This study highlights the potential of targeting cellular factors involved in RNA processing for the development of broad-spectrum antiviral agents.
Article
Neurosciences
Elisabet Jakova, Mohamed Taha Moutaoufik, Jeremy S. Lee, Mohan Babu, Francisco S. Cayabyab
Summary: This study found that adenosine and A1R receptor ligands interact with alpha-syn to modulate its aggregation and neurodegeneration. A1R agonists and drugs promoting a knot conformation of alpha-syn can cause alpha-synucleinopathy and increase neuronal degeneration, whereas A1R antagonists and drugs promoting a loop conformation of alpha-syn can be harnessed for possible neuroprotective therapies.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Multidisciplinary Sciences
Casey M. Stevens, Svitlana O. Babii, Amitkumar N. Pandya, Wei Li, Yupeng Li, Jitender Mehla, Robyn Scott, Pooja Hegde, Pavan K. Prathipati, Atanu Acharya, Jinchan Liu, James C. Gumbart, Jeffrey North, Mary Jackson, Helen I. Zgurskaya
Summary: In this study, the researchers successfully purified and reconstituted MmpL3 and CmpL1 proteins into proteoliposomes. The proteins were found to facilitate proton translocation across a phospholipid bilayer, but they differed in their pH responses and interactions with substrate mimics and inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Alla Gagarinova, Ali Hosseinnia, Matineh Rahmatbakhsh, Zoe Istace, Sadhna Phanse, Mohamed Taha Moutaoufik, Mara Zilocchi, Qingzhou Zhang, Hiroyuki Aoki, Matthew Jessulat, Sunyoung Kim, Khaled A. Aly, Mohan Babu
Summary: By studying genetic interactions among all transcription factor genes in E. coli, this research reveals condition-dependent interactions and uncovers the roles of uncharacterized transcription factors.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Khaled A. Aly, Mohamed Taha Moutaoufik, Mara Zilocchi, Sadhna Phanse, Mohan Babu
Summary: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare early-onset neurodegenerative disease caused by mutations in the SACS gene. Understanding the function of Sacsin and using ARSACS disease models can improve our knowledge of this disease. Gene correction strategies and delivery methods provide hope for the development of therapeutics for ARSACS.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Zoology
Yaa Adarkwa Darko, Olaf Voss, Peter Uetz
Summary: Species are typically described using morphological terms, but there is currently no standardization for these terms and their abbreviations. Standardization is necessary for future machine-readability of all species descriptions in biology.
Article
Microbiology
Silvia Gervasoni, Jitender Mehla, Charles R. Bergen, Inga V. Leus, Enrico Margiotta, Giuliano Malloci, Andrea Bosin, Attilio V. Vargiu, Olga Lomovskaya, Valentin V. Rybenkov, Paolo Ruggerone, Helen I. Zgurskaya
Summary: This study investigated the dynamics of MexB interactions with its ligands using machine learning, computational and experimental approaches. The results showed that MexB ligands can be effectively expelled or hindered in the transporter cycle based on their interactions with specific residues in MexB binding sites. The findings indicate that MexB ligands fit into a substrate-inhibitor spectrum depending on their physico-chemical properties. This molecular-level information is important for the rational design of new inhibitors and antibiotics less susceptible to the efflux mechanism.
Article
Chemistry, Analytical
Premkumari Kumarathasan, Nazila Nazemof, Dalibor Breznan, Erica Blais, Hiroyuki Aoki, James Gomes, Renaud Vincent, Sadhna Phanse, Mohan Babu
Summary: This study evaluated the internalization and mitochondrial effects of silica nanoparticles (SiNPs) with different sizes and surface modifications. The findings suggest that physicochemical properties are determinants of SiNP exposure-related mitochondrial effects. Mitochondrial exposures combined with proteomic analysis can serve as a new approach in risk assessment, providing insights into related toxicity mechanisms.
Review
Gastroenterology & Hepatology
Hassan Zafar, Milton H. Saier
Summary: The functional diversity of the mammalian intestinal microbiome far exceeds that of the host organism, and microbial genes contribute substantially to the well-being of the host; beneficial gut organisms can also be pathogenic when present in the gut or other locations in the body; Bacteroides metabolize polysaccharides and oligosaccharides, providing nutrition and vitamins to the host and other intestinal microbial residents.
Article
Biochemistry & Molecular Biology
Milton H. Saier, Vamsee S. Reddy, Gabriel Moreno-Hagelsieb, Kevin J. Hendargo, Yichi Zhang, Vasu Iddamsetty, Katie Jing Kay Lam, Nuo Tian, Steven Russum, Jianing Wang, Arturo Medrano-Soto
Summary: The Transporter Classification Database (TCDB) is a freely accessible reference resource providing comprehensive information about transporters from various organisms, and is the only transport protein classification database adopted by the International Union of Biochemistry and Molecular Biology. The database has seen a significant increase in proteins and transport systems since its last update in 2016, with new features including a chemical ontology for substrates, new superfamilies, and novel subclasses of transport systems.
NUCLEIC ACIDS RESEARCH
(2021)