Article
Biochemistry & Molecular Biology
Mirko M. Maksimainen, Sudarshan Murthy, Sven T. Sowa, Albert Galera-Prat, Elena Rolina, Juha P. Heiskanen, Lari Lehtio
Summary: By modifying the structure of inhibitor molecules, the selectivity was successfully shifted from poly-ADP-ribosyltransferases to mono-ADP-ribosyltransferases, and the binding modes of analogs were experimentally verified. The study demonstrates a method to differentiate compound selectivity between mono- and poly-ribosyltransferases in the human ARTD family.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Food Science & Technology
Miguel R. Lugo, Allan R. Merrill
Summary: Mono-ADP-ribosyltransferase toxins are key virulence factors produced by pathogenic bacteria to compromise target host cells. Inactivation of these toxins and enzymes with small molecule therapeutics can function as anti-virulence agents to disarm the pathogen, representing an alternative strategy to antibiotic therapy that may overcome multi-drug resistance. Work over the past two decades on developing anti-virulence compounds against mono-ADP-ribosyltransferase toxins will be discussed in this review.
Review
Microbiology
Xiaoling Su, Xiaoxing You, Haodang Luo, Keying Liang, Li Chen, Wei Tian, Zufeng Ye, Jun He
Summary: Mycoplasma pneumoniae infection leads to respiratory diseases, especially atypical pneumonia and community-acquired pneumonia, often affecting children and adults. The exotoxin CARDS TX produced by M. pneumoniae has been extensively studied for its pathogenic effects and inflammatory responses, providing a theoretical basis for further research on infection mechanisms and clinical interventions.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Maria Giulia Nizi, Mirko M. Maksimainen, Lari Lehtio, Oriana Tabarrini
Summary: Major advances have been made in defining functions for human mono-ADP-ribosylating PARP enzymes (mono-ARTs), opening up potential applications for treating diseases. The combination of structural biology and medicinal chemistry has led to the development of potent small molecule inhibitors that bind to the catalytic domain. Most of these inhibitors are still in the early stages, but some have shown promising profiles as chemical tools. A compound targeting PARP7 has even progressed to clinical trials.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Maria Giulia Nizi, Mirko M. Maksimainen, Lari Lehtio, Oriana Tabarrini
Summary: This article presents recent advances in the understanding of the functions of mono-ADP-ribosylating PARP enzymes and their potential applications in treating diseases. By combining structural biology and medicinal chemistry, researchers have successfully designed potent small molecule inhibitors. The article focuses on a specific class of inhibitors with a specific motif and analyzes the available crystal structures to develop a pharmacophore model for designing new and more specific inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Cell Biology
Palmiro Poltronieri, Angela Celetti, Luca Palazzo
Summary: NAD(+) is crucial in post-translational modification of proteins and nucleic acids, with its synthesis, degradation, and transport playing a vital role in maintaining optimal NAD(+) levels. The functional connection between NAD(+-utilizing enzymes and mono(ADP-ribosyl)ating enzymes is linked to chronic diseases.
Review
Microbiology
Shannon L. Kordus, Audrey K. Thomas, D. Borden Lacy
Summary: Clostridioides difficile produces up to three different toxins, which play a key role in the pathogenesis of colon infection. In this Review, Kordus, Thomas, and Lacy discuss the structure and function of these toxins and how this information guides new therapeutic approaches. Understanding the mechanisms of host-toxin interactions provides a foundation for developing novel strategies for the treatment and prevention of C. difficile infection.
NATURE REVIEWS MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Marion Schuller, Ivan Ahel
Summary: ADP-ribosylation is a post-translational modification of proteins that plays a crucial role in cellular processes and microbial pathogenicity. Recent studies have revealed non-canonical forms of ADP-ribosylation, including modifications of nucleic acids and the discovery of new ADP-ribose derivatives. The physiological relevance of non-canonical ADP-ribosylation deserves recognition alongside traditional protein ADP-ribosylation modification.
BIOCHEMICAL JOURNAL
(2022)
Review
Pharmacology & Pharmacy
Klaus Aktories
Summary: This narrative review presents selected findings on Clostridioides difficile toxins. It starts with a personal perspective on research about G proteins, adenylyl cyclase, and ADP-ribosylating toxins in Gunter Schultz's laboratory in Heidelberg, and then highlights milestones in C. difficile toxin research, with a focus on toxin B (TcdB). The review covers various aspects of TcdB, including its structure, receptor binding, internalization, refolding, intracellular actions, and treatment of C. difficile infection.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Agriculture, Multidisciplinary
Guoyan Wang, Senlin Qin, Yining Zheng, Chao Xia, Pei Zhang, Linxuan Zhang, Junhu Yao, Yanglei Yi, Lu Deng
Summary: T-2 toxin induces ferroptosis by inducing lipid reactive oxygen species (ROS) and downregulating SLC7A11 expression, leading to cytotoxicity. In cells deficient in SLC7A11, T-2 toxin fails to further enhance ferroptosis, indicating the critical role of SLC7A11 in T-2 toxin-induced cytotoxicity. Ferroptosis mediates T-2 toxin-induced cytotoxicity by increasing ROS and downregulating SLC7A11 expression.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Madison Turner, Kayla A. Heney, A. Rod Merrill
Summary: The study demonstrated the importance of the N-terminus of C3larvinA in its structure and function, with residues Asp(23), Ala(31), and Lys(36) playing critical roles in enzymatic activity. Analysis revealed these residues participated in a series of interactions, with Ala(31) and Lys(36) associating with a structural network of previously identified residues and Asp(23) forming novel interactions. Furthermore, the membrane translocation activity of each variant into host target cells was assessed, suggesting a potential relationship between protein dipole and target cell entry.
BIOSCIENCE REPORTS
(2021)
Article
Toxicology
David Hutin, Alexandra S. Long, Kim Sugamori, Peng Shao, Sachin Kumar Singh, Marit Rasmussen, Ninni Elise Olafsen, Solveig Pettersen, Giulia Grimaldi, Denis M. Grant, Jason Matthews
Summary: The study showed that loss of TIPARP catalytic activity increases sensitivity to TCDD-induced steatohepatitis and lethality, highlighting TIPARP as a critical negative regulator of AHR activity.
TOXICOLOGICAL SCIENCES
(2021)
Review
Microbiology
Woo-Chang Chung, Moon Jung Song
Summary: This review article summarizes the roles of PARP1 in the viral life cycle of gammaherpesviruses and the strategies used by the viruses to regulate host PARP1 activity. It also discusses the implications of understanding the interactions between PARP1 and oncogenic gammaherpesviruses, which may lead to the identification of effective therapeutic targets for associated diseases.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Sociology
Teppei Sekimizu
Summary: Hikikomori, a term for shut-ins, affects over a million people in Japan. The main issue for families is not the shut-in status, but the dependency of adult children, which is exacerbated by societal factors like labor market changes and inadequate social security. The Japanese model of welfare society, reliant on stable male employment, fails when employment is unstable, leading to the expansion of the hikikomori problem as evidence of the model's dysfunction.
INTERNATIONAL JOURNAL OF JAPANESE SOCIOLOGY
(2021)
Article
Genetics & Heredity
Jorge Roman Corona-Rivera, Izabel Maryalexandra Rios-Flores, Juan Carlos Zenteno, Christian Pena-Padilla, Katia Castillo-Reyes, Lucina Bobadilla-Morales, Alfredo Corona-Rivera, Elizabeth Acosta-Fernandez, Alejandro Bruckman-Jimenez
Summary: This article presents a Mexican family in which the son has EEC3 and the father has ADULT syndrome, both heterozygous for the p.Arg266Gln pathogenic variant in TP63. The study also reviews the clinical information of the TP63 genotype.
MOLECULAR SYNDROMOLOGY
(2023)