Article
Chemistry, Physical
Karabo Lekgau, Lerato A. Raphoko, Charity M. Lebepe, Dikgale F. Mongokoana, Tlabo C. Leboho, Thabe M. Matsebatlela, Njabulo J. Gumede, Winston Nxumalo
Summary: In this study, the design and synthesis of 6-amino-quinoxaline-alkynyl derivatives were reported, and their anti-cancer and anti-tuberculosis activities were evaluated. Molecular docking identified 11 amino-quinoxaline compounds as potential aromatase inhibitors, with three compounds showing promising anti-cancer activity against MCF-7 cells. Two compounds also exhibited inhibitory activity against aromatase. Additionally, nitro-quinoxaline derivatives displayed activity against Mycobacterium tuberculosis.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Multidisciplinary
Joana M. C. Fernandes, Albino A. Dias, Rui M. F. Bezerra
Summary: The integrated Michaelis-Menten equation (IMME) is a viable and accurate methodology for studying enzyme kinetics in the presence of product inhibition. It overcomes the inaccuracies associated with conventional curve linearization methods and provides a more coherent inhibition model and accurate kinetic constants.
APPLIED SCIENCES-BASEL
(2022)
Article
Biochemistry & Molecular Biology
Yan Liu, Fan Zhang, Ling Jiang, J. Jefferson P. Perry, Zhihe Zhao, Jiayu Liao
Summary: This study introduces a novel method to determine kinetics parameters of product inhibition using quantitative FRET(qFRET) assay, providing a convenient way to determine all kinetics parameters and a new approach to combine different measurements with mutually compatible results and errors for the first time.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Oncology
Sara Caceres, Beatriz Monsalve, Angela Alonso-Diez, Belen Crespo, Maria Jose Illera, Paloma Jimena de Andres, Gema Silvan, Juan Carlos Illera
Summary: Through experimental studies on canine and human inflammatory breast cancer, it was found that anti-aromatase and anti-sulfatase therapies have inhibitory effects on tumors in vitro, while anti-sulfatase can increase tumor progression; letrozole effectively reduces tumor progression by decreasing estrogen levels.
Article
Genetics & Heredity
Honey Pavithran, Ranjith Kumavath
Summary: The study identified 14 highly deleterious mutations in the CYP19A1 gene associated with breast cancer risk through the use of multiple computational tools. Structural and molecular studies suggested that 10 variants caused various deformities and structural disturbances of the protein. Additionally, seven novel high risk nsSNPs of the human aromatase enzyme were reported in association with the pathogenesis of human breast cancer.
JOURNAL OF GENETICS
(2021)
Article
Chemistry, Multidisciplinary
Nima Rajabi, Tobias N. Hansen, Alexander L. Nielsen, Huy T. Nguyen, Michael Baek, Julie E. Bolding, Oskar O. Bahlke, Sylvester E. G. Petersen, Christian R. O. Bartling, Kristian Stromgaard, Christian A. Olsen
Summary: In this study, potent small molecule inhibitors targeting SIRT5 were developed, which showed selective growth inhibition of leukemia cells in culture. This work demonstrates that masked isosteres of carboxylic acids can serve as viable chemical motifs for the development of inhibitors targeting mitochondrial enzymes, with potential applications beyond the sirtuin field.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Luca Mazzei, Michele Cianci, Stefano Ciurli
Summary: In this study, the inhibitory characteristics of 1,4-hydroquinone and its derivatives on two ureases were investigated, and the inhibition mechanism was elucidated. Hydroquinone covalently binds to a key residue of urease, resulting in enzyme inactivation. These findings are important for understanding the inhibition mechanism of urease and designing novel antimicrobial agents.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Thermodynamics
Zhi Li, Yue Zhang, Yimao Shen, Liwei Cheng, Bei Liu, Kele Yan, Guangjin Chen, Tianduo Li
Summary: The synergistic mechanism of KHIs and THIs in preventing methane hydrate formation involves three stages, with gas adsorption playing a dominant role. The addition of THIs to solutions containing KHIs enhances methane attraction and weakens the driving force for hydrate formation. It is suggested that the methane adsorption capacity of hybrid inhibitors should be considered in future development.
Article
Chemistry, Physical
F. Peter Guengerich, Stella A. Child, Ian R. Barckhausen, Margo H. Goldfarb
Summary: The bacterial cytochrome P450(cam) binds its substrate camphor through an induced-fit mechanism, where the enzyme changes conformation after binding the substrate. This behavior is different from other P450 enzymes that utilize a conformational selection process for substrate recognition. The accessory protein putidaredoxin has no effect on substrate binding, indicating a unique mechanism for substrate recognition by P450(cam).
Article
Engineering, Environmental
Yanzhen Liu, Yang Zhao, Yuxin Jia, Lunxiang Zhang, Lei Yang, Jiafei Zhao
Summary: Fine clay particles from a hydrate rich area in the South China Sea were found to adsorb kinetic hydrate inhibitors, leading to a weakened inhibition effect. Future dosage adjustments in marine environments should carefully consider the effects of clay-rich conditions.
CHEMICAL ENGINEERING JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
William Karsten, Leonard M. Thomas, Christian Fleming, Priscilla Seabourn, Christina Bruxvoort, Lilian Chooback
Summary: Dihydrodipicolinate synthase (DHDPS) catalyzes the initial step in the biosynthesis of L-lysine, and is a potential drug target due to its absence in mammals. Acetopyruvate is a slow-binding inhibitor of DHDPS that competes with pyruvate to form a covalent enamine complex, confirmed by spectral studies and crystal structure analysis.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Muthukumar Elangovan, Jun Ka, Boryeong Pak, Woosoung Choi, Se-Ra Oh, Suk-Won Jin, Yung Joon Yoo
Summary: Ubiquitination plays an important regulatory role in angiogenesis, with E3 enzymes being extensively studied. The role of E2 enzymes in angiogenesis is less known. Through analysis of single-cell RNA sequencing data, UBE2V1 was identified as one of the most abundantly expressed E2s in endothelial cells. Inhibition of UBE2V1 affects endothelial cell proliferation, viability, morphogenesis, and migration, and is critical for FGF2-induced angiogenesis.
Article
Chemistry, Physical
Yongkang Xi, Bradley D. Frank, Apostolos Tatas, Marko Pavlovic, Lukas Zeininger
Summary: The formation of macromolecularly enriched condensates through phase separation plays a crucial role in controlling cellular functions. In this study, a novel design strategy is reported to create calcium alginate hydrogel microreactors with complex internal architectures. The fine-control over phase separation is achieved by implementing a thermal protocol, leading to the retention of subcompartmentalized structures after gelation. These multicompartmentalized hydrogel particles allow enriched components to be selectively sequestered, which can effectively control and tune the reaction kinetics of enzyme cascades.
Article
Biochemistry & Molecular Biology
Monica Sharfin Rahman, Julian Brown, Reena Murphy, Sydney Carnes, Ben Carey, Saadyah Averick, Dominik Konkolewicz, Richard C. Page
Summary: In this study, the industrially important enzyme, Candida antarctica lipase B (CalB), was modified with various functional polymers using a grafting approach. The impact of polymer chain length on CalB activity was investigated, revealing significant enhancements for acrylamide (Am) and N,N-dimethyl acrylamide (DMAm) conjugates in both aqueous and aqueous-organic media mixtures. Furthermore, the study demonstrated a gradual increase in activity for N,N-dimethylaminopropyl-acrylamide (DMAPA) conjugates with higher organic solvent content, contrary to diminished activity observed for hydrophobic polymer-protein conjugates. Overall, this research provides insights into potential advancements in lipase production, leading to new and improved lipase bioconjugates with enhanced activity and stability.
Article
Oncology
Elena Lopez-Knowles, Simone Detre, Margaret Hills, Eugene F. Schuster, Maggie C. U. Cheang, Holly Tovey, Lucy S. Kilburn, Judith M. Bliss, John Robertson, Elizabeth Mallon, Anthony Skene, Abigail Evans, Ian Smith, Mitch Dowsett
Summary: The study aimed to assess the relationship between IHC and mRNA cut-points for ER and the biological response of primary breast cancer to aromatase inhibitor treatment. Little responsiveness was observed at IHC < 10% without distinction between < 1% and 1-10% cells positive.
BREAST CANCER RESEARCH
(2022)
Article
Clinical Neurology
Sana Tasnim, Scott G. Wilson, John P. Walsh, Dale R. Nyholt
Summary: Genome-wide association study reveals genetic correlation between migraine and thyroid dysfunction, suggesting complex causal relationships between the two traits.
Article
Biochemistry & Molecular Biology
Song Zhang, Jack A. L. Cooper, Yee Seng Chong, Alina Naveed, Chelsea Mayoh, Nisitha Jayatilleke, Tao Liu, Sebastian Amos, Simon Kobelke, Andrew C. Marshall, Oliver Meers, Yu Suk Choi, Charles S. Bond, Archa H. Fox
Summary: In neuroblastoma, the multifunctional DNA and RNA-binding protein NONO plays a complex role in regulating gene expression. It forms RNA and DNA-tethered condensates in the nucleus and undergoes phase separation modulated by nucleic acid binding. NONO mainly binds to the 5' end of pre-mRNAs and regulates the expression of super-enhancer-associated genes. Inhibiting NONO's RNA-binding or phase separation activity results in decreased expression of specific genes.
Review
Endocrinology & Metabolism
Nicole Lafontaine, Scott G. Wilson, John P. Walsh
Summary: This review summarizes the current understanding of DNA methylation (DNAm) in autoimmune thyroid disease (AITD), highlighting differential DNAm in several genes implicated in AITD. However, further replication and functional studies are needed to support the causal roles of these differential DNAm in AITD pathogenesis. Additionally, the influence of thyroid hormones on DNAm and the confounding effects of reverse causation need to be considered. Recent studies suggest a potential mechanism for the association between iodine and AITD through differential DNAm patterns in candidate genes. The research focus is shifting towards epigenome-wide studies to elucidate the role of DNAm in AITD and identify diagnostic, prognostic, and therapeutic targets.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Antoine Weihs, Layal Chaker, Tiphaine C. Martin, Kim V. E. Braun, Purdey J. Campbell, Simon R. Cox, Myriam Fornage, Christian Gieger, Hans J. Grabe, Harald Grallert, Sarah E. Harris, Brigitte Kuehnel, Riccardo E. Marioni, Nicholas G. Martin, Daniel L. McCartney, Allan F. McRae, Christa Meisinger, Joyce B. J. van Meurs, Jana Nano, Matthias Nauck, Annette Peters, Holger Prokisch, Michael Roden, Elizabeth Selvin, Marian Beekman, Diana van Heemst, Eline P. Slagboom, Brenton R. Swenson, Adrienne Tin, Pei-Chien Tsai, Andre Uitterlinden, W. Edward Visser, Henry Voelzke, Melanie Waldenberger, John P. Walsh, Anna Koettgen, Scott G. Wilson, Robin P. Peeters, Jordana T. Bell, Marco Medici, Alexander Teumer
Summary: Novel associations between thyroid hormones and DNA methylation were discovered, advancing our understanding of thyroid hormone action particularly related to KLF9. This study demonstrates the utility of integrating EWAS with other -omics data for unraveling thyroid hormone signaling in humans.
Article
Biochemistry & Molecular Biology
William J. Jowsey, Calum R. P. Morris, Drew A. Hall, John T. Sullivan, Robert D. Fagerlund, Karina Y. Eto, Paul D. Solomon, Joel P. Mackay, Charles S. Bond, Joshua P. Ramsay, Clive W. Ronson
Summary: Horizontal gene transfer in bacteria is tightly regulated by the DUF2285 domain, which is involved in both transcriptional activation and antiactivation. The DUF2285 domain interacts with other domains to control the initiation of gene transfer.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Genetics & Heredity
Bronwyn G. A. Stuckey, Timothy W. W. Jones, Bryan K. K. Ward, Scott G. G. Wilson
Summary: A 28-year-old man with congenital hypogonadotropic hypogonadism (CHH) was found to carry the GNRH1 p.R31C mutation, which was reported as pathogenic and dominant. The same mutation was found in his son at birth, but the hormonal changes associated with minipuberty were confirmed in the infant at 64 days. Further genetic sequencing identified a second variant, AMHR2 p.G445_L453del, in the patient and not in his son, suggesting a digenic cause of the patient's CHH. The observed GNRH1 mutation may not be dominant or exhibits incomplete penetrance and variable expressivity. This report highlights the importance of assessing inherited genetic disorders of hypothalamic function during the time window of minipuberty.
Article
Genetics & Heredity
Sarah Rashid, Scott G. Wilson, Kun Zhu, John P. Walsh, Jiake Xu, Benjamin H. Mullin
Summary: This study analyzed the transcriptome of human peripheral blood mononuclear cells and their differentiated osteoclast-like cells in culture, identifying differentially expressed genes and associated biological pathways in the progression of osteoporosis. Several well-established osteoclast genes were significantly upregulated in osteoporosis, and the upregulated genes were involved in cell division, migration, adhesion, as well as oxidative phosphorylation, glycolysis, lysosome, and focal adhesion pathways.
Editorial Material
Biochemical Research Methods
Elspeth F. Garman, Randy J. Read, Charles S. Bond
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2023)
Article
Instruments & Instrumentation
Stephanie A. Boer, Jason R. Price, Alan Riboldi-Tunnicliffe, Rachel Williamson, Robert Rostan, Aston Summers, Gemma F. Turner, Isabelle Jones, Charles S. Bond, Alice Vrielink, Andrew C. Marshall, John Hitchings, Stephen A. Moggach
Summary: A new high-pressure single-crystal diffraction setup has been developed and utilized at the Australian Synchrotron. This setup allows for the collection of molecular and protein crystal structures. By using a modified micro-Merrill-Bassett cell and holder, the setup can be easily integrated into the existing beamline setup, enabling high-pressure diffraction measurements.
JOURNAL OF SYNCHROTRON RADIATION
(2023)
Article
Endocrinology & Metabolism
Tessa A. Mulder, Purdey J. Campbell, Peter N. Taylor, Robin P. Peeters, Scott G. Wilson, Marco Medici, Colin Dayan, Vincent V. W. Jaddoe, John P. Walsh, Nicholas G. Martin, Henning Tiemeier, Tim I. M. Korevaar
Summary: This study found that the effects of many known thyroid function-related genes are already apparent in childhood, and some genes have a greater impact on children compared to adults. These findings provide new insights into the genetic regulation of thyroid function in early life.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2023)
Article
Plant Sciences
Sang Dang Huynh, Joanna Melonek, Catherine Colas des Francs-Small, Charles S. Bond, Ian Small
Summary: Restorer-of-fertility (Rf) genes encode pentatricopeptide repeat (PPR) proteins that target mitochondria and bind to transcripts inducing cytoplasmic male sterility. A distinct domain called RfCTD is found in most Rf proteins and is associated with cleavage of mitochondrial RNA targets. Plant genera with bisexual flowers have higher numbers of RFL genes, suggesting their role in male fertility.
Article
Microbiology
Aleksandra W. W. Debowski, Nicole M. M. Bzdyl, David R. R. Thomas, Nichollas E. E. Scott, Christopher H. H. Jenkins, Jua Iwasaki, Emily A. A. Kibble, Chen Ai Khoo, Nicolas J. J. Scheuplein, Pamela M. M. Seibel, Theresa Lohr, Georgie Metters, Charles S. S. Bond, Isobel H. H. Norville, Keith A. A. Stubbs, Nicholas J. J. Harmer, Ulrike Holzgrabe, Hayley J. J. Newton, Mitali Sarkar-Tyson
Summary: This study demonstrates that the inhibition of the Mip protein in C. burnetii can reduce its replication inside host cells, increase its sensitivity to oxidative stress, and exhibit antibiotic properties against different forms of the pathogen. Furthermore, the inhibitors show protective activity in an infection model. These findings suggest that Mip is essential for replication in C. burnetii and the development of more potent inhibitors against this protein could be a potential therapeutic approach.
Editorial Material
Biochemical Research Methods
Randy J. Read, Edward N. Baker, Charles S. Bond, Elspeth F. Garman, Mark J. van Raaij
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2023)
Article
Biology
Carolina Medina-Gomez, Benjamin H. Mullin, Alessandra Chesi, Vid Prijatelj, John P. Kemp, Chen Shochat-Carvalho, Katerina Trajanoska, Carol Wang, Raimo Joro, Tavia E. Evans, Katharina E. Schraut, Ruifang Li-Gao, Tarunveer S. Ahluwalia, M. Carola Zillikens, Kun Zhu, Dennis O. Mook-Kanamori, Daniel S. Evans, Maria Nethander, Maria J. Knol, Gudmar Thorleifsson, Ivana Prokic, Babette Zemel, Linda Broer, Fiona E. McGuigan, Natasja M. van Schoor, Sjur Reppe, Mikolaj A. Pawlak, Stuart H. Ralston, Nathalie van der Velde, Mattias Lorentzon, Kari Stefansson, Hieab H. H. Adams, Scott G. Wilson, M. Arfan Ikram, John P. Walsh, Timo A. Lakka, Kaare M. Gautvik, James F. Wilson, Eric S. Orwoll, Cornelia M. van Duijn, Klaus Bonnelykke, Andre G. Uitterlinden, Unnur Styrkarsdottir, Kristina E. Akesson, Timothy D. Spector, Jonathan H. Tobias, Claes Ohlsson, Janine F. Felix, Hans Bisgaard, Struan F. A. Grant, J. Brent Richards, David M. Evans, Bram van der Eerden, Jeroen van de Peppel, Cheryl Ackert-Bicknell, David Karasik, Erika Kague, Fernando Rivadeneira
Summary: Skull bone mineral density (SK-BMD) is a suitable trait for studying bone biology, particularly related to intramembranous ossification. A genome-wide association meta-analysis identified 59 loci associated with SK-BMD, which collectively explained 12.5% of the variance in the trait. These loci are involved in skeletal development and osteoporosis, and four of them are related to intramembranous ossification and craniofacial abnormalities.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Andrew C. Marshall, Jerry Cummins, Simon Kobelke, Tianyi Zhu, Jocelyn Widagdo, Victor Anggono, Anthony Hyman, Archa H. Fox, Charles S. Bond, Mihwa Lee
Summary: Demixing of proteins and nucleic acids into condensed liquid phases is a common mechanism in cellular organization. Proteins with low sequence complexity often form liquid-like condensates. RNA-binding proteins with prion-like regions drive condensate formation, but this study finds that the longer prion-like region of SFPQ attenuates condensation, serving a regulatory role in preventing aberrant condensate formation.
JOURNAL OF MOLECULAR BIOLOGY
(2023)