Article
Multidisciplinary Sciences
Takao Morimune, Ayami Tano, Yuya Tanaka, Haruka Yukiue, Takefumi Yamamoto, Ikuo Tooyama, Yoshihiro Maruo, Masaki Nishimura, Masaki Mori
Summary: Research has shown that the protein Tbc1d24 forms unique cellular structures called cytoophidia in neuronal cells, which are different from other types of cytoophidia. The formation of Tbc1d24 cytoophidia is influenced by cellular juvenescence and affects its enzymatic activity.
Review
Oncology
Huai-liang Wu, Yue Gong, Peng Ji, Yi-fan Xie, Yi-Zhou Jiang, Guang-yu Liu
Summary: Targeting nucleotide metabolism can enhance the immune response against tumors by activating the host immune system, increasing immunogenicity, and regulating immunity through the release of nucleoside analogs via microbes.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Chemistry, Organic
Xin Liu, Yan Fu, Qiqi Zhou, Su Wang, Lu Gao, Jiali Lei, Aibing Ke, Yeying Li, Xuexia Zhang, Changhong Huo, Xinhua Lu
Summary: Five unprecedented chromone derivatives were obtained from the fungus Aspergillus deflectus NCC0415, and their structures were identified using various techniques. The hexacyclic derivatives showed potent enzyme inhibition activity.
Article
Chemistry, Medicinal
Ling-Jie Gao, Yuan Lin, Steven De Jonghe, Mark Waer, Piet Herdewijn
Summary: Researchers prepared three different types of prodrugs of Mizoribine, and found that the ester derivatives effectively inhibited the secretion of specific immune molecules and prolonged graft survival. The combination therapy of these prodrugs with tacrolimus also showed a synergistic effect in vivo.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Letter
Clinical Neurology
Pin-Shiuan Chen, Meng-Chen Wu, Chun-Hwei Tai, Yung-Yee Chang, Min-Yu Lan, Ying-Fa Chen, Han- Lin, Ni-Chung Lee, Chin-Hsien Lin
Summary: We investigated 245 Taiwanese patients with dystonia and found no evidence to suggest a link between the inosine monophosphate dehydrogenase gene (IMPDH2) and the disease, suggesting that IMPDH2 may not play a major role in dystonia.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Oncology
Shiyu Wang, Fan Chao, Cong Zhang, Dunsheng Han, Guoxiong Xu, Gang Chen
Summary: The study found that circPFKP was significantly increased in prostate cancer tissues compared to noncancerous tissues, and was correlated with PCa risk classification, N stage, and prognostic group. CircPFKP promotes PCa cell proliferation by interacting with IMPDH2, and its production may be facilitated by hnRNPF binding.
Article
Agriculture, Multidisciplinary
Yun Wang, Tianqing Xia, Chenhao Li, Duwen Zeng, Lili Xu, Liyun Song, Hengsong Yu, Shichao Chen, Jianzhi Zhao, Xiaoming Bao
Summary: Saccharomyces cerevisiae has been identified as a preferred source for industrial production of ribonucleic acids (RNAs) and their derivatives. In this study, a modified RNA polymerase I-mediated green fluorescent protein expression system was used to screen and identify an industrial S. cerevisiae strain with an 18.2% increase in RNA content. Transcriptome analysis showed enhanced activity of genes and pathways associated with rRNA transcription, purine metabolism, and phosphate transport. The study provides valuable insights into RNA synthesis and its application in the food industry.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Bin Zhang, Yang Xu, Jinyan Liu, Chongming Wu, Xiaohong Zhao, Lidong Zhou, Yong Xie
Summary: Excessive intake of inosine 5'-monophosphate (IMP) may lead to metabolic dysfunction and lipohyperplasia in adipose tissue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medical Laboratory Technology
Xiaoyuan Jia, Yao Liu, Yan Cheng, Yin Wang, Hui Kang, Zhongren Ma, Kan Chen
Summary: This study reveals the role of IMPDH1 in promoting HCC growth and progression, and its association with patient cumulative survival.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Article
Surgery
Harisudhan Thanukrishnan, Raman Venkataramanan, Rajil B. Mehta, Dana Jorgensen, Puneet Sood
Summary: This study investigated the impact of early post-transplant pharmacokinetics and pharmacodynamics on acute rejection after renal transplantation. The research found that the partial exposures of mycophenolic acid (MPA) and Tacrolimus during the first week were more predictive of rejection than trough concentrations or exposures at 90 days. Lower MPA exposure and sub-optimal inosine monophosphate dehydrogenase (IMPDH) inhibition were associated with rejection.
CLINICAL TRANSPLANTATION
(2022)
Article
Biochemistry & Molecular Biology
Wolfgang Winnicki, Andreas Fichtenbaum, Harald Herkner, Florina Regele, Michael Baier, Sieglinde Zelzer, Ludwig Wagner, Guerkan Sengoelge
Summary: This study aimed to investigate individualized approaches to mycophenolic acid (MPA) therapy to improve clinical outcomes in renal transplant patients. The results showed that pharmacodynamic monitoring of IMPDH activity in peripheral blood cells may be an effective method for drug dose adjustment.
Review
Biochemistry & Molecular Biology
Anika L. Burrell, Justin M. Kollman
Summary: Inosine-5'-monophosphate dehydrogenase (IMPDH) is an important enzyme in purine metabolism, regulating flux at the branch point between adenine and guanine nucleotide synthesis and participating in transcription regulation. Mutations in IMPDH1 and IMPDH2 are associated with different human diseases, but their effects at the enzyme level are still unclear. Mutations in IMPDH1 lead to retinal degeneration and recent studies have revealed the molecular mechanisms behind the functional defects. IMPDH1 splice variants in the retina up-regulate guanine nucleotide synthesis by reducing sensitivity to feedback inhibition by downstream products. Understanding the role of IMPDH1 in the retina and characterizing an animal disease model will provide insights into the molecular mechanism of IMPDH1-associated blindness.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Kalpana Katiyar, Ramesh Kumar Srivastava, Ravindra Nath, Gagandeep Singh
Summary: Cryptosporidiosis, a neglected tropical disease, lacks effective therapeutic options due to limited in vitro parasite culture and lack of a reliable animal model. In this study, computational methods were used to identify novel drug-like compounds targeting the parasite enzyme CpIMPDH, which is crucial for the survival of Cryptosporidium parvum.
INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Gerardo Andres Libreros-Zuniga, Danilo Pava e Pavao, Vinicius de Morais Barroso, Nathalya Cristina de Moraes Roso Mesquita, Saulo Fehelberg Pinto Braga, Glaucius Oliva, Rafaela Salgado Ferreira, Kelly Ishida, Marcio Vinicius Bertacine Dias
Summary: Tuberculosis is a major global cause of death, and the emergence of drug-resistant strains has increased the burden of this disease. New alternative therapies are constantly needed, and recent research has identified small molecules as potential inhibitors of Ldts in M. tuberculosis, which have antimycobacterial activity.
BIOORGANIC CHEMISTRY
(2024)
Article
Pharmacology & Pharmacy
Emma Mitidieri, Valentina Vellecco, Vincenzo Brancaleone, Domenico Vanacore, Onorina L. Manzo, Emil Martin, Iraida Sharina, Yekaterina Krutsenko, Maria Chiara Monti, Elva Morretta, Andreas Papapetropoulos, Giuseppe Caliendo, Francesco Frecentese, Giuseppe Cirino, Raffaella Sorrentino, Roberta D'Emmanuele di Villa Bianca, Mariarosaria Bucci
Summary: The study found that H2S-induced contraction requires an intact eNOS/NO/sGC pathway and involves cIMP as a second messenger. The contraction effect involves a transient increase of cGMP and CAMP metabolism caused by PDE5 and PDE4A, unmasking cIMP contraction. This research provides important insights into vascular regulatory mechanisms.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biophysics
Tina Leontidou, Ziyi Yu, Jeannine Hess, Katrin Geisler, Alison G. Smith, Anthony Coyne, Chris Abell
Summary: We demonstrate the generation of novel composite hydrogel microparticles loaded with BODIPY 505/515, which can be used to deliver the dye to microalgal cells to stain the intracellular lipids. The microparticles were prepared by combining polymeric micelles with hydrogel technology to obtain microparticles of enhanced loading capacity. The method can also be used to stain other types of microalgal cells.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Article
Chemistry, Medicinal
Raghad Aljarf, Simon Tang, Douglas E. V. Pires, David B. Ascher
Summary: Teratogenic drugs can cause severe fetal malformation and have a critical impact on fetal health, but the teratogenic risks of most approved drugs are unknown. In this study, researchers propose a novel predictive tool called embryoTox, which uses a graph-based signature representation of chemical structure to predict and classify molecules that are likely to be safe during pregnancy. The tool achieved high accuracy on cross-validation and blind tests, outperforming alternative approaches. The authors believe that embryoTox will provide a practical resource for screening libraries and identifying safe molecules for use during pregnancy. The tool is freely available online at https://biosig.lab.uq.edu.au/embryotox/.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Editorial Material
Microbiology
Joicymara S. Xavier, Monika Moir, Houriiyah Tegally, Nikita Sitharam, Wasim Abdool Karim, James E. San, Joana Linhares, Eduan Wilkinson, David B. Ascher, Cheryl Baxter, Douglas E. Pires, Tulio de Oliveira
Summary: The SARS-CoV-2 Africa dashboard is a customizable tool that provides visual representation of SARS-CoV-2 genomic information in African countries. It allows users to see the number of sequences deposited in each country and track the circulating variants. This dashboard enables real-time exploration of public data to assist policymakers, healthcare professionals, and the general public in understanding the ongoing pandemic.
NATURE MICROBIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Vladimir Morozov, Carlos H. M. Rodrigues, David B. Ascher
Summary: Biologics, a rapidly expanding class of therapeutics, can have toxic properties. However, there is a lack of qualitative rules or predictive tools for assessing toxicity of peptide- and protein-based biologics. To address this, researchers have developed CSM-Toxin, an in-silico protein toxicity classifier that uses deep learning to analyze protein sequences. CSM-Toxin accurately identifies potentially toxic peptides and proteins, outperforming other methods. The researchers believe CSM-Toxin will be a valuable platform for minimizing potential toxicity in biologic development. The method is freely available as a user-friendly webserver.
Article
Chemistry, Multidisciplinary
Jamal El Bakali, Michal Blaszczyk, Joanna C. Evans, Jennifer A. Boland, William J. McCarthy, Imam Fathoni, Marcio V. B. Dias, Eachan O. Johnson, Anthony G. Coyne, Valerie Mizrahi, Tom L. Blundell, Chris Abell, Christina Spry
Summary: By performing a fragment screen, we identified three series of fragments that occupy distinct regions in the active site of MtbPPAT. Guided by X-ray crystal structures, we successfully linked weakly-binding fragments to produce an active site binder with Mtb activity, as demonstrated by CRISPR interference. This study represents a significant progress in validating MtbPPAT as a potential drug target and designing anti-TB drugs targeting MtbPPAT.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Michael Silk, Alex de Sa, Moshe Olshansky, David B. Ascher
Summary: Developmental and epileptic encephalopathies (DEEs) are a group of epilepsies with early onset and severe symptoms. It is challenging to identify causative mutations within these genes due to disease heterogeneity, but in silico predictors have improved our ability to detect possible pathogenic variants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yunzhuo Zhou, Qisheng Pan, Douglas E. Pires, Carlos H. M. Rodrigues, David B. Ascher
Summary: Understanding the effects of mutations on protein stability is crucial. We developed DDMut, a fast and accurate siamese network, to predict changes in Gibbs Free Energy upon single and multiple point mutations. DDMut achieved high correlations and outperformed most available methods. It is a useful platform for understanding the functional consequences of mutations and guiding protein engineering.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Chemistry, Multidisciplinary
Vinayak Singh, Godwin Akpeko Dziwornu, Kelly Chibale
Summary: Drug metabolism plays an important role in the treatment of tuberculosis caused by Mycobacterium tuberculosis (Mtb). Mtb has enzymes that can activate or deactivate xenobiotics, affecting treatment outcomes. Understanding the biotransformation of anti-tubercular compounds by Mtb can aid new chemical tool development, study of successful TB infections, and potential areas for drug discovery and dose optimization.
NATURE REVIEWS CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Dana Jessen-Howard, Qisheng Pan, David B. Ascher
Summary: Human aldehyde dehydrogenases (ALDHs) have a crucial role in the metabolism of both endogenous and exogenous aldehydes. Disruptions in ALDH activity can lead to the accumulation of cytotoxic aldehydes, which are associated with various diseases. This study investigates the pathogenic consequences of missense mutations in ALDHs, providing valuable insights for cancer treatment development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Carlos H. M. Rodrigues, David B. Ascher
Summary: Proteins are crucial for various biological functions, and understanding the relationship between their structure and function is essential. We present CSM-Potential2, a deep learning platform that can analyze binding interfaces on protein structures, predict protein-protein interactions and biological ligands, and allow for ligand transplantation based on sequence and structure similarity to experimentally determined structures.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Genetics & Heredity
Raghad Al-Jarf, Malancha Karmakar, Yoochan Myung, David B. Ascher
Summary: This study systematically recorded the variants of non-homologous end joining DNA repair genes and their associations with human syndromes and cancers. The impacts of these variants on protein folding, dynamics, stability, and interactions were quantitatively assessed using biophysical tools. The findings provide valuable insights into the role of NHEJ repair in genetic disorders and can inspire further investigations for the development of improved therapeutic strategies.
Article
Genetics & Heredity
Stephanie Portelli, Ruby Heaton, David B. Ascher
Summary: The development and approval of antivirals against SARS-CoV-2 has provided clinicians with treatment strategies against COVID-19, reducing deaths. However, the extensive use of these drugs can lead to antiviral resistance. This study computationally analyzed the effects of mutations on antiviral targets and identified potential resistance in different genome regions, providing insights for drug stewardship and therapeutic design.
Article
Biochemical Research Methods
Yoochan Myung, Douglas E. Pires, David B. Ascher
Summary: In this study, the researchers explored the structural features of antibody-antigen interfaces by assessing concavity and interatomic interactions. They found that complementarity-determining regions utilized deeper concavity, with nanobodies showing the deepest use of concavity. Tryptophan residues, especially in nanobodies, were found to use deeper concavity, making them suitable for targeting concave antigen surfaces. Similarly, antigens utilized arginine to bind to deeper pockets of the antibody surface. These findings contribute to a better understanding of antibody specificity and can potentially enhance the effectiveness of antibody-based therapies.
Review
Biochemistry & Molecular Biology
Sauvik Samanta, Sumit Kumar, Eswar K. K. Aratikatla, Sandeep R. R. Ghorpade, Vinayak Singh
Summary: Tuberculosis (TB) has been the deadliest infectious disease for the past 2000 years, claiming more lives than any other infectious disease. In 2021, TB caused 1.6 million deaths globally, ranking second only to COVID-19. Unfortunately, TB drug discovery research was neglected in the last few decades of the twentieth century. Recently, the World Health Organization has taken action to develop new TB drugs, with imidazopyridine being recognized as a potential drug scaffold and showing significant activity against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB).
RSC MEDICINAL CHEMISTRY
(2023)