Article
Multidisciplinary Sciences
Inchul Shin, Yifan Wang, Aimin Liu
Summary: Recent findings of TyrH and SfmD proteins resembling enzymes from the TDO superfamily have prompted a reexamination of the structure and function of this superfamily. These enzymes share a similar core architecture and histidine-ligated heme, primarily functioning to promote O-atom transfer to aromatic metabolites. The expanding boundaries of the superfamily include new members like PrnB, SfmD, TyrH, and MarE, which mediate monooxygenation on a broader set of aromatic substrates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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
Chemistry, Medicinal
Lennart Brewitz, Yu Nakashima, Sonia K. Piasecka, Eidarus Salah, Sally C. Fletcher, Anthony Tumber, Thomas P. Corner, Tristan J. Kennedy, Giorgia Fiorini, Armin Thalhammer, Kirsten E. Christensen, Mathew L. Coleman, Christopher J. Schofield
Summary: Jumonji-C domain-containing protein 5 (JMJD5) is an important 2-oxoglutarate-dependent oxygenase that has various functions in development, circadian rhythm, and cancer. This study discovered potent JMJD5 inhibitors, which are 5-aminoalkyl-substituted derivatives of the broad-spectrum 2OG oxygenase inhibitor pyridine-2,4-dicarboxylic acid (2,4-PDCA). Crystallographic analyses showed that these inhibitors bind to JMJD5 in an induced fit manner, with the C5 substituent of 2,4-PDCA binding to the substrate-binding pocket of JMJD5. Cellular studies revealed that these lead compounds displayed similar phenotypes as clinically observed JMJD5 variants with reduced catalytic activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Hematology
Jenni Maatta, Raisa Serpi, Sohvi Horkko, Valerio Izzi, Johanna Myllyharju, Elitsa Y. Dimova, Peppi Koivunen
Summary: The genetic ablation of P4H-TM was shown to protect against atherosclerosis by potentially modulating immuno-metabolic interactions, including the presence of IgM antibodies to Ox-LDL and increased lipoprotein lipase levels. This mechanism could provide a novel approach for intervention in atherosclerosis pathology by targeting hypertriglyceridemia and promoting protective immune responses.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Physiology
Andres A. Urrutia, Nan Guan, Claudia Mesa-Ciller, Aqeela Afzal, Olena Davidoff, Volker H. Haase
Summary: The study investigates the role of NG2 cells in HIF-regulated cerebral vascular homeostasis and finds that HIF2 activation in NG2 cells promotes neurovascular expansion independently of EPO. The activity of HIF2 in NG2 cells is controlled by both PHD2 and PHD3, and PHD1 modulates HIF2 transcriptional responses when PHD2 and PHD3 are inactive.
Article
Biochemistry & Molecular Biology
Franziska Dengler, Sofia Sova, Antti M. Salo, Joni M. Maki, Peppi Koivunen, Johanna Myllyharju
Summary: HIF prolyl 4-hydroxylases (HIF-P4H) control the powerful mechanism regulating cellular adaptation to decreased oxygenation and the gastrointestinal epithelium has a well-designed control over this adaptation. The gene expression levels of HIF pathway components were found to be higher towards the distal end of the gastrointestinal tract, with HIF-P4H-2 playing a predominant role in the gut epithelium. These findings suggest the development of selective inhibitors targeting specific HIF-P4H isoforms may be useful for diverging therapeutic needs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Nadiya Byts, Subodh Sharma, Jenny Laurila, Prodeep Paudel, Ilkka Miinalainen, Veli-Pekka Ronkainen, Reetta Hinttala, Kid Tornquist, Peppi Koivunen, Johanna Myllyharju
Summary: Prolyl 4-hydroxylases (P4Hs) are crucial in regulating collagen synthesis and response to hypoxia. A newly identified member, transmembrane P4H (P4H-TM), plays a key role in calcium signaling and gliotransmission regulation. Loss of function mutations in P4H-TM can lead to severe intellectual disability syndrome.
Article
Chemistry, Inorganic & Nuclear
Reza Latifi, Taryn D. Palluccio, Wanhua Ye, Jennifer L. Minnick, Kwame S. Glinton, Elena Rybak-Akimova, Sam P. de Visser, Laleh Tahsini
Summary: This study investigates the reactivity of biomimetic nonheme iron(IV) oxo complex towards olefin epoxidation through a combination of experimental and computational approaches. The results show that pH significantly affects the oxygen-atom-transfer reaction and the identity of the axial ligand influences the catalytic activity. Computational studies suggest that the change in OAT is due to electrostatic interactions of the pendant amine cation.
INORGANIC CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Dechao Feng, Li Li, Dengxiong Li, Ruicheng Wu, Weizhen Zhu, Jie Wang, Luxia Ye, Ping Han
Summary: The study found that P4HB may serve as a prognostic biomarker and predict radiotherapy resistance in prostate cancer patients. Downregulation of P4HB expression can inhibit the proliferation of prostate cancer cells.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Jeffrey W. Slater, Chi-Yun Lin, Monica E. Neugebauer, Molly J. McBride, Debangsu Sil, Mrutyunjay A. Nair, Bryce J. Katch, Amie K. Boal, Michelle C. Y. Chang, Alexey Silakov, Carsten Krebs, J. Martin Bollinger
Summary: An aliphatic halogenase requires four substrates: 2-oxoglutarate(2OG), halide (Cl- or Br-), the halogenation target (prime substrate), and dioxygen. The binding of 2OG, halide, and l-Lys to the cofactor of the enzyme activates the Fe(II) for O-2 capture and initiates its conversion to a haloferryl complex. The mechanistic data of BesD suggest that it may have evolved from a hydroxylase ancestor and the acquisition of its activity involves a linkage between l-Lys binding and chloride coordination.
Article
Urology & Nephrology
Volker H. Haase
Summary: HIF-PHIs are a promising new class of orally administered drugs for the treatment of anemia of chronic kidney disease. They activate the HIF oxygen-sensing pathway, promoting erythropoiesis and modulating iron metabolism to potentially reduce the need for i.v. iron supplementation. These drugs are predicted to have effects beyond erythropoiesis.
KIDNEY INTERNATIONAL SUPPLEMENTS
(2021)
Article
Biochemistry & Molecular Biology
Su Liu, Yanmei Li, Meng Wang, Yi Ma, Jufang Wang
Summary: Collagen, the most abundant protein in the human body, has wide applications in biomedical and tissue engineering fields. However, its large-scale exogenous production is hindered by complex posttranslational modifications. In this study, a novel prolyl hydroxylated recombinant collagen with good biocompatibility and thermal stability was developed. The hydroxylated collagen showed significant improvements compared to nonhydroxylated recombinant collagen. This study provides a promising method for further development of collagen application in biomaterials engineering.
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Xiulai Chen, Juyang Yi, Wei Song, Jia Liu, Qiuling Luo, Liming Liu
Summary: Chassis engineering was used to enhance enzymatic production of Hyp in Escherichia coli, leading to significant improvements in Hyp titre, conversion rate and productivity. Rewiring the TCA cycle and l-proline degradation pathway increased alpha-ketoglutarate supply, while fine-tuning heterologous haemoglobin expression improved oxygen transfer, resulting in a more efficient method for industrial production of Hyp.
MICROBIAL BIOTECHNOLOGY
(2021)
Article
Oncology
Juesheng Yang, Jiajun Xu, Lei Tao, Shiyong Wang, Haiyan Xiang, Yanhua Tang
Summary: This study found that remote ischemic preconditioning (RIP) and prolyl 4-hydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG) exerted synergistic protective effects on myocardial injury induced by ischemia/reperfusion (I/R). Mechanistically, these protective effects were achieved through the activation of HIF-1 alpha and its downstream VEGF/AKT-eNOS signaling pathway.
MOLECULAR MEDICINE REPORTS
(2022)
Article
Biochemical Research Methods
Fitzya Y. Bocanegra-Jimenez, Gabriela M. Montero-Moran, Samuel Lara-Gonzalez
Summary: XanA is a unique enzyme in fungi responsible for converting xanthine to uric acid. In this study, the XanA enzyme from Aspergillus oryzae was successfully purified in its active form from E. coli bacteria, and its optimal activity conditions were determined.
PROTEIN EXPRESSION AND PURIFICATION
(2021)
Article
Biochemistry & Molecular Biology
Aubrey J. Ellison, I. Caglar Tanrikulu, Jesus M. Dones, Ronald T. Raines
Article
Biology
Lindsey R. F. Backman, Yolanda Y. Huang, Mary C. Andorfer, Brian Gold, Ronald T. Raines, Emily P. Balskus, Catherine L. Drennan
Review
Chemistry, Multidisciplinary
Bianca-Vanesa Boros, Vasile Ostafe
Article
Chemistry, Medicinal
Chelcie H. Eller, Ronald T. Raines
ACS INFECTIOUS DISEASES
(2020)
Article
Biochemical Research Methods
Jessica Sayers, Evans C. Wralstad, Ronald T. Raines
Summary: The ribonuclease S complex has led to historic discoveries in protein chemistry and enzymology, but its applications have been hindered by two main drawbacks: immune response in humans and susceptibility to dissociation. By semi-synthesizing an RNase S conjugate derived from human pancreatic ribonuclease and stabilized with a covalent interfragment cross-link, these limitations have been addressed, enabling unprecedented applications of the RNase-S system.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Gheorghita Menghiu, Vasile Ostafe, Radivoje Prodanovic, Rainer Fischer, Raluca Ostafe
Summary: Chitinases catalyze the degradation of chitin, a polymer found in various organisms. Developing improved chitinases is important for addressing environmental concerns and potential applications of chitosan products. This study focused on creating a high-throughput screening system and selecting enhanced chitinase variants by utilizing fluorescence-activated cell sorting and mutagenesis techniques.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Agronomy
Diana Larisa Roman, Denisa Ioana Voiculescu, Madalina Filip, Vasile Ostafe, Adriana Isvoran
Summary: Research shows that the effects of triazole fungicides are dose-dependent, with high doses strongly impacting the structure of microbial communities in soil and typically decreasing both the population of soil microbes and the activities of enzymes in the soil.
Article
Biochemistry & Molecular Biology
Sayani Chattopadhyay, Leandro B. C. Teixeira, Laura L. Kiessling, Jonathan F. McAnulty, Ronald T. Raines
Summary: This study provides a method to upregulate the TGF-beta signaling pathway by clustering the extracellular domains of TGF-beta receptors, which can enhance wound healing.
ACS CHEMICAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Emily R. Garnett, Ronald T. Raines
Summary: Pancreatic-type ribonucleases (ptRNases) are a family of vertebrate-specific secretory endoribonucleases that catalyze the degradation of RNA substrates and mediate biological functions. Two ptRNases, RNase 1 and angiogenin, are known to be involved in inflammation, blood coagulation, neovascularization, cancer, amyotrophic lateral sclerosis, and cellular stress response. Further research is ongoing to elucidate the biology of these and other ptRNases.
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Infectious Diseases
Ian W. Windsor, Dawn M. Dudley, David H. O'Connor, Ronald T. Raines
Summary: By engineering amino acid substitutions in RNase 1, it has been transformed into a zymogen that can be activated by HIV-1 protease, showing high toxicity towards infected cells.
AIDS RESEARCH AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Linus B. Boll, Ronald T. Raines
Summary: The position of Cys in a protein sequence can be exploited to improve site-selectivity in maleimide-based modifications, while differences in the reactivity of Lys towards an NHS ester are modest.
Meeting Abstract
Biochemistry & Molecular Biology
Lindsey R. F. Backman, Yolanda Y. Huang, Mary C. Andorfer, Brian Gold, Ronald T. Raines, Emily P. Balskus, Catherine L. Drennan
Article
Biochemistry & Molecular Biology
Denisa Ioana Voiculescu, Diana Larisa Roman, Vasile Ostafe, Adriana Isvoran
Summary: Difenoconazole is a chemical compound with four stereoisomers and has been found in agricultural products and drinking water. A computational approach has been used to evaluate the toxicological effects of these stereoisomers. The results show that all the stereoisomers have toxic effects on humans, such as inhibiting cytochromes, hepatotoxicity, neurotoxicity, mutagenicity, skin sensitization potential, and endocrine disrupting effects. There are small differences in the predicted probabilities of producing various biological effects between the different stereoisomers.
Article
Biochemistry & Molecular Biology
Diana Larisa Roman, Denisa Ioana Voiculescu, Mariana Adina Matica, Victor Baerle, Marioara Nicoleta Filimon, Vasile Ostafe, Adriana Isvoran
Summary: This study investigated the effects of triticonazole on soil microorganisms, enzymes, and human health. Results showed that triticonazole decreased enzyme activities and the total number of soil microorganisms. Both stereoisomers of triticonazole were found to bind to human plasma proteins and potentially inhibit human cytochromes, leading to cardiotoxicity and low endocrine disruption potential. Specifically, (R)-TTZ caused skin sensitization, carcinogenicity, and respiratory toxicity.
Article
Biochemistry & Molecular Biology
Constantina Bianca Vulpe, Mariana Adina Matica, Renata Kovacevic, Daniela Dascalu, Zoran Stevanovic, Adriana Isvoran, Vasile Ostafe, Gheorghita Menghiu
Summary: The aim of this research was to investigate the bioremediation conditions of copper in synthetic water. Various genetically modified strains of Saccharomyces cerevisiae, Pichia pastoris, and Escherichia coli were used to determine the copper ions accumulation efficiency. The E. coli BL21 RIL strain had the best copper accumulation efficiency, which was 1250 times more efficient than the control strain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Saranya Krishnan, Shina Sasi, Preshobha Kodakkattumannil, Salima Al Senaani, Geetha Lekshmi, Martin Kottackal, Khaled M. A. Amiri
Summary: This study aimed to develop an efficient DNA extraction protocol suitable for diverse plant species and tissues. A reliable and consistent protocol was described for the extraction of high-quality DNA from difficult-to-extract plant species. The optimized protocol was successful in extracting high-quality DNA from various plant species and tissues, making it useful for genomic studies of recalcitrant plants.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Eisaku Hokazono, Saori Fukumoto, Takeshi Uchiumi, Susumu Osawa
Summary: This study proposes a method for detecting nucleic acid amplification using pyrophosphate, which requires only two reagents and an automated analyzer. The technique has high sensitivity and reproducibility, and can detect pyrophosphate within 10 minutes. Therefore, this method has the potential to be a new, rapid, and simple detection technique for amplified nucleic acids.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Drew S. Sowersby, L. Kevin Lewis
Summary: SURE electrophoresis is a new method for concentrating samples in gels, which allows efficient detection of highly dilute DNA samples. This approach generates single bands with enhanced signal intensities and minimal band broadening.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Hongyi Liang, Guoliang Yin, Guangxi Shi, Zhiyong Liu, Xiaofei Liu, Jingwei Li
Summary: The mechanism of Echinacoside (ECH) in treating breast cancer (BC) was explored through network pharmacology and experimental validation. It was found that ECH plays an important role in anti-BC by regulating the PI3K/AKT/HIF-1 alpha/VEGF signaling pathway, and it exhibits multi-target and multi-pathway effects.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Daniel S. Kantner, Emily Megill, Anna Bostwick, Vicky Yang, Carmen Bekeova, Alexandria Van Scoyk, Erin L. Seifert, Michael W. Deininger, Nathaniel W. Snyder
Summary: This study compared the results of different methods for measuring the amount of acetyl-Coenzyme A. The colorimetric ELISA kit did not produce interpretable results, while the fluorometric enzymatic kit showed comparable results to the LC-MS-based methods depending on the matrix and extraction conditions. LC-MS/MS and LC-HRMS methods produced well-aligned results, especially when using stable isotope-labeled internal standards.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Jingyan Xu, Hanying Tan, Xionghui Ma, Linjing Su, Zhi Zhang, Yuhao Xiong
Summary: This study investigates the co-catalytic capabilities of MoO3 nanosheets in enhancing the enzyme-like catalytic activity of a two-dimensional ultrathin Fe(III)-modified covalent triazine framework (Fe-CTF) under neutral pH conditions. The Fe-CTF/MoO3 co-catalytic system exhibits enzyme-mimicking activity and enables the development of a colorimetric method for glucose detection. Furthermore, a straightforward one-pot colorimetric method is established for screening XOD inhibitors.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Lichao Zhang, Kang Xiao, Xueting Wang, Liang Kong
Summary: A novel fusion technology was designed to identify FAD-binding sites, achieving the best results on two independent test datasets and outperforming existing methods significantly. The high performance and certainty of the method were demonstrated through statistical tests and cross-entropy loss analysis.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Abdulkadir Kilic, Mehmet Aslan, Abdulkadir Levent
Summary: This study developed a simple, rapid, sensitive, and selective voltammetric technique for the electrochemical characterization and detection of the highly risky drug Edoxaban. The optimized voltammetric method showed good analytical working range and was successfully applied to urine and tablet samples.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Su Hyun Kim, Nara Shin, Jong-Min Jeon, Jeong-Jun Yoon, Jeong Chan Joo, Hee Taek Kim, Shashi Kant Bhatia, Yung-Hun Yang
Summary: To address environmental issues caused by traditional plastics, bioplastics have gained attention as alternatives. Although bioplastics have better degradability, their degradation still takes longer than anticipated. This study proposes a novel screening method to identify bioplastic degraders faster, saving time and providing more quantitative data.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Irem Okman Kocoglu, Pinar Esra Erden, Esma Kilic
Summary: In this study, an electrochemical biosensor based on carbon nanofibers and ionic liquid modification was constructed for tyramine detection. The biosensor showed linear response, low detection limit, high sensitivity, and exhibited good reproducibility, stability, and anti-interference ability.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Liana U. Akhmetzianova, Timur M. Davletkulov, Assol R. Sakhabutdinova, Alexey Chemeris, Irek M. Gubaydullin, Ravil R. Garafutdinov
Summary: A new program called LAMPrimers iQ has been developed for high-quality LAMP primer design, and its advantages in providing higher specificity and reliable detection of viral RNA were validated using SARS-CoV-2 coronavirus RNA as a model target.
ANALYTICAL BIOCHEMISTRY
(2024)
Article
Biochemical Research Methods
Tommaso Pileri, Alberto Sinibaldi, Agostino Occhicone, Norbert Danz, Elena Giordani, Matteo Allegretti, Frank Sonntag, Peter Munzert, Patrizio Giacomini, Francesco Michelotti
Summary: This study developed a biosensing device based on one-dimensional photonic crystal to detect HER2 in breast cancer. The device combines label-free and fluorescence operation modes, allowing for real-time and accurate detection in less than 20 minutes. It offers a promising technique for combined label-free and fluorescence detection in disease diagnosis and therapeutic monitoring.
ANALYTICAL BIOCHEMISTRY
(2024)