Article
Microbiology
Wassihun Wedajo Aragaw, Nicole Cotroneo, Suzanne Stokes, Michael Pucci, Ian Critchley, Martin Gengenbacher, Thomas Dick
Summary: SPR719 targets DNA gyrase in NTM and displays differential resistance development in Mycobacterium avium and Mycobacterium abscessus, with the latter possibly involving drug efflux in high-frequency resistance.
MICROBIOLOGY SPECTRUM
(2022)
Article
Multidisciplinary Sciences
Mohammad Javad Taghipour, Hamid Ezzatpanah, Mohammad Ghahderijani
Summary: This study isolated camel milk protein fractions and hydrolyzed them using enzymes, finding peptides with anticancer and antibacterial activities. Two promising peptides, P3 and P5, showed low binding energy and inhibition constant, making them potential drug candidates.
Article
Biochemistry & Molecular Biology
German Pozdeev, Aalap Mogre, Charles J. Dorman
Summary: DNA gyrase, composed of GyrA and GyrB subunits, plays a crucial role in bacterial physiology. The positioning of gyrase genes can affect various functions within the bacteria, with a particular impact on virulence genes like SPI-2. Understanding the significance of gene arrangements in bacteria can provide insights into genome evolution and the sensitivity of certain genes to disruptions in DNA topology.
MOLECULAR MICROBIOLOGY
(2021)
Article
Infectious Diseases
Jong-Hoon Park, Tomoyuki Yamaguchi, Yuki Ouchi, Kentaro Koide, Ruttana Pachanon, Joseph Yamweka Chizimu, Shigetarou Mori, Hyun Kim, Tetsu Mukai, Chie Nakajima, Yasuhiko Suzuki
Summary: The study demonstrated that WQ-3334 and WQ-3810 showed higher inhibitory activity against Mycobacterium leprae DNA gyrase, with WQ-3334 exhibiting stronger activity against quinolone-resistant strains. The R1 group was found to play a crucial role in molecular interactions, suggesting that enhancing binding affinity with different R8 group molecules could improve the inhibitory effect of new fluoroquinolones on drug-resistant bacteria.
MICROBIAL DRUG RESISTANCE
(2021)
Article
Multidisciplinary Sciences
Ilias Georgakopoulos-Soares, Chengyu Deng, Vikram Agarwal, Candace S. Y. Chan, Jingjing Zhao, Fumitaka Inoue, Nadav Ahituv
Summary: The grammar of gene regulation is challenging to understand, which hinders our ability to connect genotype with phenotype. In this study, the researchers used massively parallel reporter assays to examine over 200,000 synthetic sequences, revealing that the order and orientation of transcription factor binding sites (TFBS) significantly impact gene regulatory activity.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Martina Durcik, Andrej Emanuel Cotman, Zan Toplak, Stefan Mozina, Ziga Skok, Petra Eva Szili, Marton Czikkely, Elvin Maharramov, Thu Hien Vu, Maria Vittoria Piras, Nace Zidar, Janez Ilas, Anamarija Zega, Jurij Trontelj, Luis A. Pardo, Diarmaid Hughes, Douglas Huseby, Talia Berruga-Fernandez, Sha Cao, Ivailo Simoff, Richard Svensson, Sergiy V. Korol, Zhe Jin, Francisca Vicente, Maria C. Ramos, Julia E. A. Mundy, Anthony Maxwell, Clare E. M. Stevenson, David M. Lawson, Bjorn Glinghammar, Eva Sjostrom, Martin Bohlin, Joanna Oreskar, Sofie Alver, Guido V. Janssen, Geert Jan Sterk, Danijel Kikelj, Csaba Pal, Tihomir Tomasic, Lucija Peterlin Masic
Summary: A new series of dual low nanomolar benzothiazole inhibitors of bacterial DNA gyrase and topoisomerase IV were developed, exhibiting broad-spectrum antibacterial activities against various strains. Lead compound 7a showed favorable properties and selectivity for bacterial topoisomerases, and demonstrated efficacy in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ying Yu, Junsong Guo, Zhengjun Cai, Yingchen Ju, Jun Xu, Qiong Gu, Huihao Zhou
Summary: This study utilized fragment screening and X-ray crystallography to identify new building blocks and binding mechanisms for the discovery of new GyrB inhibitors. Some chemical fragments were found to affect enzyme activity, providing new insights for the design of GyrB inhibitors.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
S. Behera, Pragyan P. Dash, Ajit K. Bishoyi, K. Dash, P. Mohanty, Chita R. Sahoo, Rabindra N. Padhy, M. Mishra, B. N. Ghosh, H. Sahoo, B. R. Jali
Summary: Resistance to antibiotics and antifungal drugs has become a common public health threat, leading to the need for alternative, non-toxic agents. This study designed and synthesized two novel antibiotic molecules, which showed significant inhibitory activity against bacterial strains and fungal strains. Molecular docking studies revealed their potential targets, and binding interaction with a serum protein was also observed. Furthermore, the toxicity analysis indicated their non-cytotoxic nature.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Multidisciplinary
Cheng-Jie Ma, Lin Li, Wen-Xuan Shao, Jiang-Hui Ding, Xiao-Li Cai, Zhao-Rong Lun, Bi-Feng Yuan, Yu-Qi Feng
Summary: 5-Hydroxymethyluracil (5hmU) is a thymine modification found in various organism genomes. A novel enzyme-mediated bioorthogonal labeling method has been developed to selectively enrich 5hmU in genomes, allowing for a better understanding of its distribution and functional roles.
Article
Hematology
Fatma Isik Ustok, James A. Huntington
Summary: The prothrombinase complex processes prothrombin to thrombin through sequential cleavage, with the order of cleavage determined by the presence or absence of cofactor and membrane. The docking of prothrombin on factor Va plays a crucial role in determining the cleavage order, with Arg320 being presented for initial cleavage. The a1-loop sequence also plays a critical role in prothrombin binding and cleavage.
Article
Biochemistry & Molecular Biology
Samuel Godfrey Hendrix, Kuan Y. Chang, Zeezoo Ryu, Zhong-Ru Xie
Summary: Developing a new, reliable prediction method of DNA binding sites is crucial for future research, as current methods show relatively poor accuracy. By utilizing 3D coordinates and atom-type information, a deep learning model was trained to predict DNA-binding sites on protein surfaces, which outperformed previous methods and demonstrated robust performance across different evaluation datasets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Infectious Diseases
Hani A. Alhadrami, Raha Orfali, Ahmed A. Hamed, Mohammed M. Ghoneim, Hossam M. Hassan, Ahmed S. Hassane, Mostafa E. Rateb, Ahmed M. Sayed, Noha M. Gamaleldin
Summary: Flavonoid-coated gold nanoparticles show enhanced antibacterial activity, with quercetin-coated GNPs being the most effective, able to penetrate bacterial cell walls. In silico experiments explain the conjugation efficiency and antibacterial mechanisms of these bioactive compounds.
Article
Biochemistry & Molecular Biology
Galal Magdy, Fathalla Belal, Ahmed Faried Abdel Hakiem, Ahmed M. Abdel-Megied
Summary: In this study, the binding interaction of cabozantinib with salmon sperm DNA (SS-DNA) was investigated under simulated physiological conditions using multiple experimental methods. The results indicated that cabozantinib binds to SS-DNA through hydrophobic and hydrogen bonding interactions, primarily via minor groove binding. Molecular docking analysis showed that cabozantinib fits into the AT-rich region of the B-DNA minor groove with a binding site of 4 base pairs long. Additionally, the flexibility of cabozantinib's structure, with eight active torsions, played a significant role in forming a stable cabozantinib-DNA complex.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Dimitrios Avgoulas, Georgios Katsipis, Eleftherios Halevas, Elena G. Geromichalou, George D. Geromichalos, Anastasia A. Pantazaki
Summary: The oxovanadium (IV)-curcumin complex showed interaction with albumin and DNA, with a single high-affinity binding site for albumin and good hemocompatibility. It binds to DNA through a minor groove mode with a high apparent binding constant. The complex also demonstrated a strong binding constant value to DNA with Stern-Volmer quenching phenomenon.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Paptawan Thongdee, Yoshinobu Nagura, Haruna Sabishiro, Naruedon Phusi, Darunee Sukchit, Pharit Kamsri, Auradee Punkvang, Khomson Suttisintong, Pornpan Pungpo, Noriyuki Kurita
Summary: This study investigated the specific interactions between GyrB residues and pyrrolamide derivatives and designed potent inhibitors against GyrB. The results showed strong hydrogen bonds and electrostatic interactions between the derivatives and GyrB, indicating their potential as effective GyrB inhibitors.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Multidisciplinary
Joanna Czescik, Susanna Zamolo, Tamis Darbre, Riccardo Rigo, Claudia Sissi, Adam Pecina, Laura Riccardi, Marco De Vivo, Fabrizio Mancin, Paolo Scrimin
Summary: Gold nanoparticles can efficiently catalyze chemical reactions as nanozymes, exhibiting the highest efficiency in cleaving plasmid DNA. By successfully mimicking the suggested structure of natural metallonucleases, this study provides important insights into the catalytic mechanism.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Biochemistry & Molecular Biology
Shannon J. McKie, Keir C. Neuman, Anthony Maxwell
Summary: DNA topoisomerases are essential for cellular survival, playing numerous roles in DNA metabolism. Structural approaches and single-molecule techniques have provided new insights into their interaction and mechanism, while the importance of interactions with other proteins has been highlighted. Novel topoisomerases like topo VIII and Mini-A are expanding our understanding of DNA processes and the vital functions they perform.
Article
Biochemistry & Molecular Biology
Silvia Da Ros, Giulia Nicoletto, Riccardo Rigo, Silvia Ceschi, Eleonora Zorzan, Mauro Dacasto, Mery Giantin, Claudia Sissi
Summary: The regulation of conformational arrangements of gene promoters is a crucial physiological mechanism for fine control of gene expression. By studying the G-quadruplex forming sites in the KIT promoter, it was found that different G4 sites impact SP1 binding and protein expression levels, with kit2 and kit* serving as an on-off system for KIT expression. Using two G4 binders could potentially target kit2-kit* as a reliable pharmacological intervention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Anja Kolaric, Thomas Germe, Martina Hrast, Clare E. M. Stevenson, David M. Lawson, Nicolas P. Burton, Judit Voros, Anthony Maxwell, Nikola Minovski, Marko Anderluh
Summary: The researchers designed a series of novel NBTIs with improved DNA gyrase-binding moieties, demonstrating their ability to stabilize single-strand cleavage complexes through asymmetric intercalation. Experimental evidence was provided to confirm the previously postulated mechanism of action.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Lipeng Feng, Julia E. A. Mundy, Clare E. M. Stevenson, Lesley A. Mitchenall, David M. Lawson, Kaixia Mi, Anthony Maxwell
Summary: The research demonstrates that MfpA in Mycobacterium smegmatis modulates the activity of gyrase by interacting with the enzyme, protecting it from the effects of drugs. This provides a reference for understanding the mechanism of action of other pentapeptide-repeat proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Enrico Buglione, Domenico Salerno, Claudia Adriana Marrano, Valeria Cassina, Guglielmo Vesco, Luca Nardo, Mauro Dacasto, Riccardo Rigo, Claudia Sissi, Francesco Mantegazza
Summary: This study analyzed the nanomechanical properties of three G4s in the promoter of the KIT proto-oncogene using magnetic tweezers, identifying a characteristic fingerprint of G4 folding under negative supercoiling. It also examined the energetic contribution of G4 to the double-strand denaturation process and observed a reduction in the energy required for strands separation in the presence of negative supercoiling.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Guglielmo Vesco, Marco Lamperti, Domenico Salerno, Claudia Adriana Marrano, Valeria Cassina, Riccardo Rigo, Enrico Buglione, Maria Bondani, Giulia Nicoletto, Francesco Mantegazza, Claudia Sissi, Luca Nardo
Summary: Utilizing fluorescence resonance energy transfer, the folding of expressly designed constructs with G-quadruplexes flanked by double stranded DNA segments was investigated both in ensemble and at the single molecule level. The presence of flanking ends was found to bias both the final equilibrium state and the folding kinetics of the G-quadruplexes. This previously unconsidered aspect sheds light on the complex relationships involved in fine tuning the gene-regulatory properties of DNA structures.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Medicinal
Alberto Ongaro, Giovanni Desiderati, Erika Oselladore, Davide Auricchio, Maurizio Memo, Giovanni Ribaudo, Claudia Sissi, Alessandra Gianoncelli
Summary: This study found that guanine-rich sequences can form G-quadruplex structures in oncogenes and telomeres, inhibiting immortalization of cancer cells. Researchers improved ligand design based on an anthraquinone scaffold using click chemistry to enhance side chain length and interactions with nucleobases, leading to increased stability and selectivity towards G4 DNA.
Editorial Material
Chemistry, Medicinal
Kyle M Orritt, Anthony Maxwell, Colin WG Fishwick, Martin J McPhillie
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Harriet C. C. Gooch, Raymond Kiu, Steven Rudder, David J. Baker, Lindsay J. Hall, Anthony Maxwell
Summary: Four bacterial strains isolated from the wax moth Galleria mellonella were characterized as a potential new species Enterococcus innesii, through a polyphasic approach including 16S rRNA gene sequence analysis, core-genome analysis, and various phenotypic analyses. The strains showed close relation to Enterococcus casseliflavus and Enterococcus gallinarum, but further analysis revealed distinct genomic characteristics and low similarity with the closest phylogenetic relative, leading to the proposal of a new species designation.
INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY
(2021)
Article
Biology
Shannon J. McKie, Parth Rakesh Desai, Yeonee Seol, Adam M. B. Allen, Anthony Maxwell, Keir C. Neuman
Summary: DNA topoisomerase VI (topo VI) is a type IIB DNA topoisomerase predominantly found in archaea and some bacteria, as well as plants and algae. It has been discovered that topo VI preferentially decatenates DNA crossings by having a preference for certain DNA crossing geometries. Additionally, topo VI exhibits increased ATPase activity, DNA binding, and rate of strand passage with increasing DNA writhe, providing further evidence that it acts as a DNA crossing sensor. The study suggests that topo VI has evolved an intrinsic preference for the unknotting and decatenation of interlinked chromosomes by sensing and preferentially unlinking DNA crossings with geometries close to 90 degrees.
Editorial Material
Biochemistry & Molecular Biology
Manlio Palumbo, Claudia Sissi
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Masa Sterle, Martina Durcik, Clare E. M. Stevenson, Sara R. Henderson, Petra Eva Szili, Marton Czikkely, David M. Lawson, Anthony Maxwell, Dominique Cahard, Danijel Kikelj, Nace Zidar, Csaba Pal, Lucija Peterlin Masic, Janez Ilas, Tihomir Tomasic, Andrej Emanuel Cotman, Anamarija Zega
Summary: We have developed a new series of DNA gyraseB inhibitors based on 2-aminobenzothiazole, showing promising activity against ESKAPE bacterial pathogens. The chemical space of the benzothiazole-based series was expanded to the C5 position of the benzothiazole ring, resulting in compound E with low nanomolar inhibition of DNA gyrase and broad-spectrum antibacterial activity. Computational analysis revealed that substitution at position C5 can enhance the inhibitory potency of the compounds and modify their physicochemical properties.
Article
Biochemistry & Molecular Biology
Kyle M. Orritt, Lipeng Feng, Juliette F. Newell, Jack N. Sutton, Scott Grossman, Thomas Germe, Lauren R. Abbott, Holly L. Jackson, Benjamin K. L. Bury, Anthony Maxwell, Martin J. McPhillie, Colin W. G. Fishwick
Summary: By 2050, antimicrobial resistance is likely to cause 10 million global deaths annually, resulting in a massive economic burden. However, the discovery of a new medicinal chemistry strategy targeting a different binding site on DNA gyrase may provide a way to overcome this problem. Through computer-based molecular design methods, a series of novel compounds were synthesized and evaluated for their activity. The reported structure-activity relationships offer important insights for further exploration of this new binding site.
RSC MEDICINAL CHEMISTRY
(2022)
