Review
Clinical Neurology
Haotian Liu, Yong Xie, Xia Wang, Martine Abboud, Chao Ma, Wei Ge, Christopher J. Schofield
Summary: The article discusses the potential roles of 2OGDD in AD, highlighting the relationship with synaptic dysfunction/loss and the importance of regulating neuronal/glial differentiation through enzyme activity-dependent mechanisms to protect against synaptic loss.
ALZHEIMERS & DEMENTIA
(2022)
Article
Chemistry, Inorganic & Nuclear
Lennart Brewitz, Yu Nakashima, Anthony Tumber, Eidarus Salah, Christopher J. Schofield
Summary: The synthesis of F- and CF(3-)substituted derivatives of the broad-spectrum 2OG oxygenase inhibitor pyridine-2,4-dicarboxylate (2,4-PDCA) was reported, showing that the introduction of F- or CF3-substituent at the C5 position can substantially increase selectivity for AspH over KDM4E. Crystallographic studies provided insights into the structural basis of this observation, demonstrating how a small change in a 2OG analogue can have a significant impact on 2OG oxygenase inhibition efficacy.
JOURNAL OF FLUORINE CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Matthew E. Cockman, Yoichiro Sugimoto, Hamish B. Pegg, Norma Masson, Eidarus Salah, Anthony Tumber, Helen R. Flynn, Joanna M. Kirkpatrick, Christopher J. Schofield, Peter J. Ratcliffe
Summary: JMJD6 is a 2-oxoglutarate-dependent dioxygenase involved in various cellular processes. Through mass spectrometry analysis, we identified 150 lysine hydroxylation sites on 48 protein substrates catalyzed by JMJD6, including 19 hydroxylation sites on BRD4. Most of these substrates are associated with membraneless organelle formation, suggesting a potential role for JMJD6 in regulating subcellular partitioning in response to stress.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Michael Batie, Temitope Fasanya, Niall S. Kenneth, Sonia Rocha
Summary: Oxygen is crucial for mammalian organisms' viability, and cells activate various signaling cascades to survive and adapt to changes in oxygen availability. These cascades lead to alterations in chromatin, gene expression, metabolism, and viability, which are often mediated by post-translational modifications (PTMs). The direct impact of changes in oxygen availability on PTMs, such as proline, asparagine, histidine, and lysine hydroxylation, lysine and arginine methylation, and cysteine dioxygenation, is reviewed in this article, with a focus on mammalian systems. Additionally, indirect effects on phosphorylation, ubiquitination, and sumoylation in response to hypoxia are discussed. The coordination of direct and indirect oxygen-regulated changes to PTMs is critical for the cell's response to hypoxia, but further research is needed to understand the specific oxygen sensitivity and functional relevance of certain PTMs.
Article
Biochemistry & Molecular Biology
Joanna Bonnici, Razanne Oueini, Eidarus Salah, Catrine Johansson, Christopher J. J. Schofield, Akane Kawamura
Summary: We found that the catalytic domains of all human KDM5s, KDM4E, and to a lesser extent KDM4A/D, exhibit both lysine demethylase (KDM) and arginine demethylase (RDM) activities on histone peptides. Ras GTPase-activating protein-binding protein 1 peptides are substrates for KDM5C/D RDM. This study highlights the potential of JmjC-KDMs to catalyze reactions beyond N-epsilon-methyllysine demethylation. Although limited to peptide fragments, our results provide guidance for biological studies investigating JmjC functions.
Article
Cell Biology
Jian Zhou, Suling Bo, Hao Wang, Lei Zheng, Pengfei Liang, Yongchun Zuo
Summary: A prediction model OGFE_RAAC was developed to identify 2OG oxygenases, achieving an accuracy of 91.04% with excellent generalization and robustness. This model is expected to become an effective tool for the identification of 2OG oxygenases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Yu-Hsuan Hsiao, Szu-Jo Huang, En-Chi Lin, Po-Yun Hsiao, Shu-Ing Toh, I-Hsuan Chen, Zhengren Xu, Yu-Pei Lin, Hsueh-Ju Liu, Chin-Yuan Chang
Summary: In this study, the substrate binding environment and substrate specificity of the non-heme iron oxygenase CmnC were investigated through biochemical characterization and structural determination. Among CmnC and its homologues VioC and OrfP, only OrfP exhibited the ability to hydroxylate the substrate enantiomer d-Arg. Mutagenesis analysis revealed the importance of specific residues in the substrate binding pocket for substrate stereoselectivity. This study provides insights into the enzyme engineering of non-heme iron oxygenases for adjusting substrate stereoselectivity and developing biocatalysts.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Radoslaw P. Nowak, Anthony Tumber, Eline Hendrix, Mohammad Salik Zeya Ansari, Manuela Sabatino, Lorenzo Antonini, Regina Andrijes, Eidarus Salah, Nicola Mautone, Francesca Romana Pellegrini, Klemensas Simelis, Akane Kawamura, Catrine Johansson, Daniela Passeri, Roberto Pellicciari, Alessia Ciogli, Donatella Del Bufalo, Rino Ragno, Mathew L. Coleman, Daniela Trisciuoglio, Antonello Mai, Udo Oppermann, Christopher J. Schofield, Dante Rotili
Summary: New MINA53 inhibitors have been successfully identified, showing selective effects on cancer cells and antiproliferative activity, and enhancing the sensitivity of cancer cells to conventional chemotherapy drugs. These findings provide potential for further exploration of the role of MINA53 inhibitors in combination therapies.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Plant Sciences
Akiyoshi Yoda, Xiaonan Xie, Kaori Yoneyama, Kenji Miura, Christopher S. P. McErlean, Takahito Nomura
Summary: Seeds of root parasitic plants are induced to germinate by strigolactones exudated from host roots. The biosynthesis pathway of 5-deoxystrigol, a major strigolactone, has not been fully understood. In this study, researchers identified Sobic.005G213500 as a regulator that affects the stereoselective biosynthesis of 5-deoxystrigol and provides insights into how different strigolactones are produced to combat parasitic weed infestations.
PLANT AND CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Luigi Scietti, Elisabetta Moroni, Daiana Mattoteia, Marco Fumagalli, Matteo De Marco, Lisa Negro, Antonella Chiapparino, Stefano A. Serapian, Francesca De Giorgi, Silvia Faravelli, Giorgio Colombo, Federico Forneris
Summary: Overexpression of LH/PLOD enzymes in the tumor microenvironment leads to abnormal accumulation of collagen post-translational modifications, which is correlated with increased metastatic progression of solid tumors. The chelating agent 2,2'-bipyridil unexpectedly enhances the enzymatic activity of LH by reducing the inhibitory effect of excess Fe2+. This finding provides new insights for drug discovery targeting LH/PLOD.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yujuan Wang, Yaoyao Zhang, Zehua Li, Junfeng Wang
Summary: JMJD8 is a protein from the JMJD family with only the JmjC domain. Studies have shown that JMJD8 is involved in signaling pathways like AKT/NF-kappa B, affecting cell proliferation and development. Results reveal that JMJD8 acts as a non-histone demethylase, specifically demethylating AKT1 and altering its protein function by changing its methylation level.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Reito Bunno, Takayoshi Awakawa, Takahiro Mori, Ikuro Abe
Summary: This study elucidates the biosynthesis of 2-aminoisobutyric acid (AIB) in Penicillium, demonstrating a novel pathway involving the enzymes TqaL, TqaF, and TqaM for the formation of AIB, expanding the catalytic repertoire of Fe-II/alpha KG oxygenases. The unique aziridine ring opening by a HAD-type hydrolase and oxidative decarboxylation by a non-heme iron oxygenase are key steps in this process.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Pharmacology & Pharmacy
Stephin Baby, Durgesh Gurukkala Valapil, Nagula Shankaraiah
Summary: Epigenetic enzyme-targeted therapy is a promising development in drug discovery, with histone deacetylases and DNA methyltransferases being investigated as druggable targets. Recently, histone methyltransferases and lysine demethylase inhibitors have become the focus of clinical trials as potential epi-drugs. KDM4 enzymes, part of the 2-OG-dependent oxygenases group, have attracted attention as novel targets in cancer therapy, with efforts being made to develop selective small molecule inhibitors.
DRUG DISCOVERY TODAY
(2021)
Article
Chemistry, Multidisciplinary
Bingnan Wang, Yong Lu, Lide Cha, Tzu-Yu Chen, Philip M. Palacios, Liping Li, Yisong Guo, Wei-chen Chang, Chuo Chen
Summary: In this study, it was discovered that mononuclear nonheme iron(II) and 2-oxoglutarate (Fe/2OG)-dependent oxygenases and halogenases can catalyze diverse oxidative reactions, including hydroxylation, halogenation, epoxidation, and desaturation. In addition to known reactions, these enzymes were found to catalyze the Mukaiyama hydration, which proceeds via a hydrogen atom transfer pathway without involvement of 2OG. Unlike conventional inorganic catalysts, the Fe/2OG enzymes utilize a mononuclear iron center for this reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biotechnology & Applied Microbiology
Ryotaro Hara, Yuta Nakajima, Hiroaki Yanagawa, Ryo Gawasawa, Izumi Hirasawa, Kuniki Kino
Summary: Enzymatic synthesis of beta-Hydroxy-alpha-amino acids using the newly discovered enzyme AEP14369 from Sulfobacillus thermotolerans Y0017 has shown regioselectivity and stereoselectivity, producing high yields of the desired compounds. This achievement opens the way for practical production of beta-hydroxy-alpha-amino acids and contributes to the diversification of pharmaceutical structures, providing a sustainable and economical industrial application for these important compounds.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Vivienne Chan, Stefanie K. Novakowski, Simon Law, Christa Klein-Bosgoed, Christian J. Kastrup
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2015)
Article
Biochemistry & Molecular Biology
E. P. Booy, M. Meier, N. Okun, S. K. Novakowski, S. Xiong, J. Stetefeld, S. A. McKenna
NUCLEIC ACIDS RESEARCH
(2012)
Article
Biochemistry & Molecular Biology
Evan P. Booy, Ryan Howard, Oksana Marushchak, Emmanuel O. Ariyo, Markus Meier, Stefanie K. Novakowski, Soumya R. Deo, Edis Dzananovic, Joerg Stetefeld, Sean A. McKenna
NUCLEIC ACIDS RESEARCH
(2014)
Article
Multidisciplinary Sciences
S. Novakowski, K. Jiang, G. Prakash, C. Kastrup
SCIENTIFIC REPORTS
(2019)
Article
Hematology
Lih Jiin Juang, Nima Mazinani, Stefanie K. Novakowski, Emily N. P. Prowse, Martin Haulena, David Gailani, Leslie M. Lavkulich, Christian J. Kastrup
Article
Pediatrics
Stefanie K. Novakowski, Olive Kabajaasi, Mai-Lei Woo Kinshella, Yashodani Pillay, Teresa Johnson, Dustin Dunsmuir, Katija Pallot, Jessica Rigg, Nathan Kenya-Mugisha, Bernard Toliva Opar, J. Mark Ansermino, Abner Tagoola, Niranjan Kissoon
Summary: This study aims to understand user perspectives on the usability, feasibility, and acceptability of the digital triaging platform Smart Triage. Through face-to-face interviews, the study found that health workers found Smart Triage to be usable and feasible, and reported its positive impact on reducing treatment time for emergency pediatric cases and improving quality of care. However, challenges such as high staff turnover, lack of medical supplies, and staff attitudes limit its feasibility and acceptability.
Article
Pediatrics
Alishah Mawji, Edmond Li, Dustin Dunsmuir, Clare Komugisha, Stefanie K. Novakowski, Matthew O. Wiens, Tagoola Abner Vesuvius, Niranjan Kissoon, J. Mark Ansermino
Summary: In resource limited settings, a nine-variable triage model with high sensitivity and specificity has been developed to aid in the rapid identification of critically ill children.
FRONTIERS IN PEDIATRICS
(2022)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)