Article
Chemistry, Medicinal
Zachary W. Davis-Gilbert, Andreas Kraemer, James E. Dunford, Stefanie Howell, Filiz Senbabaoglu, Carrow I. Wells, Frances M. Bashore, Tammy M. Havener, Jeffery L. Smith, Mohammad A. Hossain, Udo Oppermann, David H. Drewry, Alison D. Axtman
Summary: Naphthyridine-based inhibitors were synthesized to produce a potent and cell active inhibitor of casein kinase 2 (CK2). Compound 2 selectively inhibits CK2 alpha and CK2 alpha ' when broad-profiled, making it an exquisitely selective chemical probe for CK2. A negative control, compound 7, lacking a key hinge-binding nitrogen, was designed based on structural studies and showed excellent kinome-wide selectivity by not binding CK2 alpha or CK2 alpha ' in cells. Compound 2 displayed differential anticancer activity compared to a structurally distinct CK2 chemical probe, SGC-CK2-1.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Biochemistry & Molecular Biology
John E. Chojnowski, Rongrong Li, Tiffany Tsang, Fatimah H. Alfaran, Alexej Dick, Simon Cocklin, Donita C. Brady, Todd I. Strochlic
Summary: Casein kinase 2 (CK2) is an evolutionarily conserved enzyme involved in cellular functions, and its dysregulation is linked to diseases like cancer. This study demonstrates that copper enhances CK2 activity by binding directly to the enzyme. Specific residues in the catalytic subunit are critical for copper-binding. Changes in cellular copper levels also affect CK2 activity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Microbiology
Sabrin R. M. Ibrahim, Alaa A. Bagalagel, Reem M. Diri, Ahmad O. Noor, Hussain T. Bakhsh, Yosra A. Muhammad, Gamal A. Mohamed, Abdelsattar M. Omar
Summary: In this study, the CK2 inhibitory activity of 33 fungal phenalenones was explored using computational studies. Compound 19 showed higher binding affinity and made additional contacts with distant amino acid residues from the active site.
Article
Biochemistry & Molecular Biology
Nhu Nguyen Quynh Tran, Kwang-Hoon Chun
Summary: KD025 is a ROCK2 isoform-specific inhibitor that inhibits adipocyte differentiation by inhibiting CK2. It shows comparable binding affinity to CK2 alpha and effectively inhibits CK2 at nanomolar concentrations. Both CX-4945 and KD025 act specifically in the middle stage of adipocyte differentiation, indicating that they may regulate the same target, CK2.
Article
Biochemistry & Molecular Biology
K. Chojnacki, D. Lindenblatt, P. Winska, M. Wielechowska, C. Toelzer, K. Niefind, M. Bretner
Summary: New halogenated 1H-triazolo [4,5-b] pyridines and 1H-imidazo [4,5-b] pyridines were synthesized as analogues of known CK2 inhibitors, with di- and trihalogenated 1H-triazolo [4,5-bl] pyridines showing the highest activity against CK2 alpha. Compounds were also evaluated for their effect on the viability of cancer cell lines, and crystal structures of complexes with CK2 alpha and CK2 alpha' were obtained.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
David W. Litchfield, Laszlo Gyenis, Daniel Menyhart, Scott E. Roffey
Summary: Advances in phosphoproteomics and the development of selective chemical probes have created new opportunities for understanding the cellular landscape of substrates for CSNK2, and potentially guiding CSNK2-targeted therapy development.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2023)
Article
Oncology
Xixi Zhao, Yongkun Wei, Yu-Yi Chu, Yintao Li, Jung-Mao Hsu, Zhou Jiang, Chunxiao Liu, Jennifer L. Hsu, Wei-Chao Chang, Riyao Yang, Li-Chuan Chan, Jingkun Qu, Shuqun Zhang, Haoqiang Ying, Dihua Yu, Mien-Chie Hung
Summary: This study reveals the role of CK2 in immunosuppression by phosphorylation and stabilization of PD-L1, and suggests CK2 inhibition as a potential immunotherapeutic approach for treating cancer.
Article
Chemistry, Medicinal
Alexander Schnitzler, Karsten Niefind
Summary: CK2, a Ser/Thr kinase, has a specific acidic substrate recognition sequence and is inhibited by polyanionic substances like heparin. This study describes the crystal structures of CK2 in complex with different heparin fragments, which provide insights into the inhibitory mechanism of heparin fragments and their chain length-dependent efficacy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Konrad Chojnacki, Patrycja Winska, Olena Karatsai, Miroslawa Koronkiewicz, Malgorzata Milner-Krawczyk, Monika Wielechowska, Maria Jolanta Redowicz, Maria Bretner, Pawel Borowiecki
Summary: The newly synthesized compounds showed potent cytotoxic activities against breast cancer cells, with methyl group derivatives more efficiently reducing cell viability. Compounds with higher logP values were found to be more effective intracellular inhibitors of CK2 with better proapoptotic properties.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Francesca Zonta, Christian Borgo, Camila Paz Quezada Meza, Ionica Masgras, Andrea Rasola, Mauro Salvi, Lorenzo A. Pinna, Maria Ruzzene
Summary: CK2, an overexpressed Ser/Thr protein kinase in many cancers, plays a crucial role in the uncontrolled proliferation, motility, and survival of cancer cells. This study reveals that both CK2 alpha and alpha' isoforms contribute to cell proliferation, survival, and tumorigenicity, with a prominent role for CK2 alpha in tumor metabolism.
Review
Biochemistry & Molecular Biology
May-Britt Firnau, Angela Brieger
Summary: In this study, evidence from literature is compiled to suggest that CK2 modulates all hallmarks of cancer, thereby promoting oncogenesis and operating as a cancer driver by creating a cellular environment favorable to neoplasia.
Review
Biochemistry & Molecular Biology
Scott E. Roffey, David W. Litchfield
Summary: CK2, an acidophilic serine/threonine kinase, regulates various biological processes such as apoptosis and cell proliferation. Studies have linked CK2 to human malignancies and diseases, but the mechanisms regulating CK2 activity remain incompletely understood.
Article
Virology
Ailyn C. Ramon, George Perez, Evelin Caballero, Mauro Rosales, Daylen Aguilar, Dania Vazquez-Blomquist, Yassel Ramos, Arielis Rodriguez-Ulloa, Viviana Falcon, Maria Pilar Rodriguez-Molto, Ke Yang, Yasser Perera, Silvio E. Perea
Summary: CIGB-325 shows antiviral activity against bovine coronavirus in vitro and interacts physically with viral proteins and a group of CK2 cellular substrates.
Article
Biochemistry & Molecular Biology
Fredrick J. Rosario, Anand Chopra, Kyle Biggar, Theresa L. Powell, Madhulika B. Gupta, Thomas Jansson
Summary: The mechanisms underlying restricted growth in intrauterine growth restriction (IUGR) are not fully understood. The mTOR signaling pathway acts as a placental nutrient sensor and indirectly affects fetal growth by regulating placental function. In this study, we found that inhibition of trophoblast mTOR increased the secretion and phosphorylation of liver IGFBP-1, which decreased the bioavailability of IGF-1 and inhibited fetal growth. This suggests that placental mTOR signaling may play a role in regulating fetal growth by controlling liver IGFBP-1 phosphorylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Eleanor L. Atkinson, Jessica Iegre, Claudio D'Amore, Paul Brear, Mauro Salvi, Marko Hyvonen, David R. Spring
Summary: In this study, an iterative cycle of enzymatic assays, X-ray crystallography, molecular modelling and cellular assays was used to develop a functionalisable chemical probe for the investigation of CK2α/β PPI. The lead peptide, P8C9, showed successful binding to CK2α at the PPI site, and it was found to be easily synthesizable and functionalisable. The peptide also exhibited high stability in serum and had potential for further optimization.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Fulvio Celsi, Lorenzo Monasta, Giorgio Arrigoni, Ilaria Battisti, Danilo Licastro, Michelangelo Aloisio, Giovanni Di Lorenzo, Federico Romano, Giuseppe Ricci, Blendi Ura
Summary: This study identified potential biomarkers in endometrial cancer using mass spectrometry and Western blotting analysis. Suprabasin, a previously associated oncogene, showed differential expression in tissue and serum samples, indicating its potential as a novel biomarker for endometrial cancer. Data mining analysis further supported the proteomic findings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Christian Borgo, Claudio D'Amore, Valeria Capurro, Valeria Tomati, Elvira Sondo, Federico Cresta, Carlo Castellani, Nicoletta Pedemonte, Mauro Salvi
Summary: The advent of Trikafta has revolutionized the treatment of cystic fibrosis patients with the most common misfolding mutation, F508del-CFTR. However, there is still room for improvement in its efficacy, especially in rare CFTR mutations. By targeting the misfolding detection machinery, the combination of Trikafta with a drug like TAK-243 shows promising results in improving CFTR function, including in rare CF-causing mutations.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Valeria Scalcon, Alessandra Folda, Maria Giovanna Lupo, Federica Tonolo, Naixuan Pei, Ilaria Battisti, Nicola Ferri, Giorgio Arrigoni, Alberto Bindoli, Arne Holmgren, Lucia Coppo, Maria Pia Rigobello
Summary: This study reveals the specific role of mitochondrial Grx2 in the regulation of cell metabolism and highlights an unknown association between Grx2 and metabolic dysfunction-associated fatty liver disease (MAFLD).
Article
Plant Sciences
Marija Vidovic, Ilaria Battisti, Ana Pantelic, Filis Morina, Giorgio Arrigoni, Antonio Masi, Sonja Veljovic Jovanovic
Summary: This study aimed to identify key candidates and pathways involved in desiccation tolerance in the resurrection plant Ramonda serbica Panc. The results showed that almost all differentially abundant proteins related to photosynthetic processes were less abundant in desiccated leaves, while chlorophyll fluorescence measurements implied shifting from linear PET to cyclic electron transport. The levels of H2O2 scavenging enzymes and other antioxidant enzymes were reduced, but certain proteins associated with germination, stress response, and cell wall remodeling were induced by desiccation. This comprehensive study contributes to understanding the role and regulation of the main metabolic pathways during desiccation, which could lead to improvements in crop drought tolerance.
Article
Biochemistry & Molecular Biology
Barbara Di Camillo, Lucia Puricelli, Elisabetta Iori, Gianna Maria Toffolo, Paolo Tessari, Giorgio Arrigoni
Summary: Protein turnover rate is crucial for cellular functions and dysregulation of protein degradation can lead to various diseases. Studying protein synthesis and degradation rates is important to understand the pathophysiology of diseases. This study used a dynamic-SILAC approach to investigate protein turnover and abundance in a cellular model of diabetic nephropathy, identifying several proteins with altered turnover and abundance between diabetic nephropathic subjects and controls. These proteins could potentially serve as biomarkers or therapeutic targets for diabetic complications. The data obtained also provide valuable information on protein half-lives in human fibroblasts and contribute to basic cell biology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Diana Piol, Laura Tosatto, Emanuela Zuccaro, Eric N. Anderson, Antonella Falconieri, Maria J. Polanco, Caterina Marchioretti, Federica Lia, Joseph White, Elisa Bregolin, Giovanni Minervini, Sara Parodi, Xavier Salvatella, Giorgio Arrigoni, Andrea Ballabio, Albert R. La Spada, Silvio C. E. Tosatto, Fabio Sambataro, Diego L. Medina, Udai B. Pandey, Manuela Basso, Maria Plennuto
Summary: Spinal and bulbar muscular atrophy is caused by polyglutamine expansions in androgen receptor, leading to gain-of-function toxicity. This study investigates the phosphorylation of polyglutamine-expanded receptor and its role in neurodegeneration. The researchers find that certain kinases and phosphatases can modify the function and toxicity of the receptor, and targeting these enzymes can potentially be used as a therapeutic approach.
Article
Food Science & Technology
Lucia Giagnoni, Saptarathi Deb, Alessandra Tondello, Giulia Zardinoni, Michele De Noni, Cinzia Franchin, Alice Vanzin, Giorgio Arrigoni, Antonio Masi, Piergiorgio Stevanato, Alessio Cecchinato, Andrea Squartini, Carlo Spanu
Summary: Cheese production relies on the complex dynamics of microbial groups, especially the proportion of psychrotrophic bacteria in milk, affected by refrigeration temperature. Accidental thermal variations of milk can occur during collection and transportation. A trial was conducted to analyze the impact of temperature on cheese quality and bacterial communities using DNA extraction and sequencing. Shifts in bacterial communities were observed, providing insights for improved handling of technical processing conditions in the cheese manufacturing industry.
FOOD RESEARCH INTERNATIONAL
(2023)
Letter
Oncology
Andrea Marranci, Antonella Prantera, Simona Masotti, Raffaella De Paolo, Caterina Baldanzi, Maurizio S. S. Podda, Serena Mero, Marianna Vitiello, Cinzia Franchin, Mariavittoria Laezza, Laura Comelli, Giorgio Arrigoni, Tiziana Cervelli, Giovanna Del Pozzo, Laura Poliseno
Summary: Our study reveals that PARP1 can down-regulate the translation of BRAF-X1, negatively impacting the MAPK pathway and sensitizing melanoma cells to BRAF and MEK inhibitors, both in vitro and in vivo.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Valeria Capaci, Giorgio Arrigoni, Lorenzo Monasta, Michelangelo Aloisio, Giulia Rocca, Giovanni Di Lorenzo, Danilo Licastro, Federico Romano, Giuseppe Ricci, Blendi Ura
Summary: This study focuses on the phosphoproteome of endometrial cancer (EC) and normal endometrium, aiming to identify differentially phosphorylated proteins involved in tumorigenic signaling pathways. Differentially phosphorylated proteins were analyzed using 2D-DIGE, IMAC, and mass spectrometry. Validation through Western blotting confirmed altered abundance of HBB, CKB, LDHB, and HSPB1. Bioinformatic analysis revealed tumorigenic signaling pathways. This study highlights the role of phosphoproteome in EC tumor growth and suggests potential for new drugs targeting EC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Agriculture, Multidisciplinary
Alice Vanzin, Cinzia Franchin, Giorgio Arrigoni, Ilaria Battisti, Antonio Masi, Andrea Squartini, Vittoria Bisutti, Diana Giannuzzi, Luigi Gallo, Alessio Cecchinato, Sara Pegolo
Summary: The study analyzed the peptidome profiles of milk samples from cows with subclinical mastitis induced by different pathogens. The results showed that the peptides that best distinguish positive from negative samples are mainly derived from abundant milk proteins such as beta- and alpha(s1)-casein, indicating the potential of these peptides as new diagnostic and therapeutic tools.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biochemical Research Methods
Nathaniel Kwok, Zita Aretz, Sumiko Takao, Zheng Ser, Paolo Cifani, Alex Kentsis
Summary: Recent advances in nucleic acid sequencing and mass spectrometry proteomics have enabled genome-scale analysis of genetic variation and transcription as well as whole proteome-scale studies of protein expression. However, most proteomic studies are limited to canonical protein sequences. Here, we develop ProteomeGenerator2 (PG2), which integrates genome and transcriptome sequencing to incorporate protein variants and other non-canonical features caused by genomic and transcriptomic variation. PG2 has been benchmarked using synthetic data and analysis of human leukemia cells and can be used with current and emerging sequencing technologies, assemblers, variant callers, and mass spectral analysis algorithms. It is open-source and available at https://github.com/kentsisresearchgroup/ProteomeGenerator2.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Eleanor L. Atkinson, Jessica Iegre, Claudio D'Amore, Paul Brear, Mauro Salvi, Marko Hyvonen, David R. Spring
Summary: In this study, an iterative cycle of enzymatic assays, X-ray crystallography, molecular modelling and cellular assays was used to develop a functionalisable chemical probe for the investigation of CK2α/β PPI. The lead peptide, P8C9, showed successful binding to CK2α at the PPI site, and it was found to be easily synthesizable and functionalisable. The peptide also exhibited high stability in serum and had potential for further optimization.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Trang Van Tran, Hoa Nguyen, Luyen Vu, ChangWoo Lee
Summary: Glutaredoxin 3 (Grx3) is a redox protein that maintains structural integrity and glutathione (GSH) binding capabilities across different temperatures. This study investigates the roles of specific bonds in Grx3's structure and function, and how psychrophilic Grx3 variants adapt to cold environments. The highly conserved Arg51-Asp69 salt bridge and Gln56-His63 hydrogen bond are crucial for stabilizing the structure and catalytic activity of Grx3. Psychrophilic variants of Grx3 have adapted to cold environments by reducing GSH binding and increasing structural flexibility.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Amanda Lais de Souza Coto, Arthur Alexandre Pereira, Sabrina Dorta Oliveira, Milene Nobrega de Oliveira Moritz, Arthur Moraes Franco da Rocha, Paulo Roberto Dores-Silva, Noeli Soares Melo da Silva, Ana Rita de Araujo Nogueira, Lisandra Marques Gava, Thiago Vagas Seraphim, Julio Cesar Borges
Summary: J-domain proteins form a large molecular chaperone family involved in proteostasis processes, with hDjC20 playing a vital role in mitochondria and being heavily influenced by the presence of Zn+2.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Meiling Zhang, Jiaxiang Zhang, Yan Liang, Shicheng Tian, Shuyang Xie, Tong Zhou, Qin Wang
Summary: This study determined the crystal structures of RGLG2 VWA domain in Arabidopsis thaliana, revealing that Ca2+ ions act as regulators and affect the conformational change of RGLG2-VWA domain.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Alexandra Bork, Sander H. J. Smits, Lutz Schmitt
Summary: This study reveals the structure and calcium ion binding properties of CBL1 protein, and proposes a binding model of CBL1 for Ca2+. Additionally, it provides preliminary insights into the formation of the dimer interface of CBL1.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Evgeniia V. Leisi, Andrey V. Moiseenko, Sofia S. Kudryavtseva, Denis V. Pozdyshev, Vladimir I. Muronetz, Lidia P. Kurochkina
Summary: The pathogenesis of prion diseases involves the transformation of prion protein into an insoluble form. This study found that two phage chaperonins can promote the fibrillation of prion protein in an ATP-dependent manner, resulting in the formation of less toxic large clusters. These fibrils differ in morphology and properties from those formed spontaneously in acidic pH with denaturants.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Gaurab Chowdhury, Saroj Biswas, Yuthika Dholey, Puja Panja, Sumit Das, Subrata Adak
Summary: Magnesium is an important divalent cation for regulating enzyme activity. The binding of Mg2+ through the PAS domain inhibits phosphoglycerate kinase (PGK) activity in LmPAS-PGK at neutral pH, but PGK activity is derepressed at acidic pH. Mutation studies revealed that the Asp-4 residue is crucial for Mg2+ binding at neutral pH.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Shima Ghaedizadeh, Majid Zeinali, Bahareh Dabirmanesh, Behnam Rasekh, Khosrow Khajeh, Ali Mohammad Banaei-Moghaddam
Summary: Implementing hyperthermostable carbonic anhydrases into CO2 capture and storage technologies can increase the rate of CO2 absorption from industrial flue gases. This study successfully improved the thermostability of a known hyperthermostable carbonic anhydrase through rational engineering of a single-point mutation.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)
Article
Biochemistry & Molecular Biology
Khaled A. Elnahriry, Dorothy C. C. Wai, Lauren M. Ashwood, Muhammad Umair Naseem, Tibor G. Szanto, Shaodong Guo, Gyorgy Panyi, Peter J. Prentis, Raymond S. Norton
Summary: Sea anemone venom contains a peptide called Tst2, which shows sequence similarity to peptides that interact with various ion channels. Recombinant Tst2 was successfully produced and its structure and function were studied. The results showed that Tst2 is an inhibitor of the TRPV1 channel.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2024)