Article
Biology
Yanmin Zhang, Sourav Chowdhury, Joao Rodrigues, Eugene Shakhnovich
Summary: A new compound CD15-3 was discovered to inhibit both the wild type and TMP-resistant variants of E. coli DHFR; CD15-3 showed delayed resistance compared to TMP in in vitro evolution; Resistance to CD15-3 was attributed to gene duplication of efflux pumps, resulting in weak resistance.
Article
Chemistry, Physical
Priyanka Singh, An Vandemeulebroucke, Jiayue Li, Cindy Schulenburg, Gabriel Fortunato, Amnon Kohen, Donald Hilvert, Christopher M. Cheatum
Summary: In the evolution of enzymes, the temperature dependence of the chemical step decreases gradually, indicating a reduction in the average donor-acceptor distance for hydride transfer and an increase in catalytic efficiency. Particularly noteworthy is the significant role played by residues distant from the active site in optimizing the chemical step of the complex, multistep enzymatic pathway.
Article
Biochemistry & Molecular Biology
Himadri S. Sarkar, Takato Mashita, Toshiyuki Kowada, Satoshi Hamaguchi, Toshizo Sato, Kento Kasahara, Nobuyuki Matubayasi, Toshitaka Matsui, Shin Mizukami
Summary: The authors developed a series of photoswitchable inhibitors selective for Escherichia coli dihydrofolate reductase (eDHFR) by modifying the structure of a previously reported compound, azoMTX. The addition of bulky bis-alkylated arylazopyrazole groups increased selectivity towards eDHFR over human DHFR. The new ligands showed nearly complete Z-to-E photoconversion and high thermostability, allowing for real-time control of eDHFR activity by switching the illumination light wavelengths.
ACS CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jiacong Li, Mingxia Yang, Weijia Li, Chujie Lu, Deyu Feng, Zhuo Shang, Chengyuan Wang, Wei Lin
Summary: This study reveals the structure of the non-canonical MTHFR MSMEG_6649 and demonstrates that it has a larger binding groove with FAD compared to canonical MTHFR. The NADH-binding site in MSMEG_6649 is similar to the FAD binding site in canonical MTHFR, suggesting NADH plays the same role in catalysis. Critical residues involved in NADH and substrate binding were identified, providing insights for understanding the catalytic mechanism and potential drug targets.
BIOCHEMICAL JOURNAL
(2023)
Article
Infectious Diseases
Stephanie J. Ambrose, Ruth M. Hall
Summary: Accurate identification of individual genes is essential for tracking the spread of antibiotic resistance genes, with trimethoprim resistance genes being increasingly found in genome sequences. This study explains common issues and pitfalls in dfrA gene identification and compiles complete information on dfrA genes/DfrA proteins in Gram-negative bacteria, proposing a method to prevent future duplication of gene numbers and confusion.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Food Science & Technology
Erton Gomes da Silva, Leonardo Ereno Tadielo, Thiago Henrique Belle, Emanoelli Aparecida Rodrigues dos Santos, Jhennifer Arruda Schmiedt, Fabio Sossai Possebon, Juliano Goncalves Pereira, Luciano dos Santos Bersot
Summary: This study found that reducing the water flow in the final wash of chicken slaughter process does not affect the microbiological quality of the chicken carcasses.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Madhu Sudan Manna, Yusuf Talha Tamer, Ilona Gaszek, Nicole Poulides, Ayesha Ahmed, Xiaoyu Wang, Furkan C. R. Toprak, DaNae R. Woodard, Andrew Y. Koh, Noelle S. Williams, Dominika Borek, Ali Rana Atilgan, John D. Hulleman, Canan Atilgan, Uttam Tambar, Erdal Toprak
Summary: The study shows that 4'-desmethyltrimethoprim (4'-DTMP) inhibits both bacterial dihydrofolate reductase (DHFR) and a common TMP-resistant variant, slowing down the evolution of antibiotic resistance in E. coli.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Ebru Cetin, Tandac F. Guclu, Isik Kantarcioglu, Ilona K. Gaszek, Erdal Toprak, Ali Rana Atilgan, Burcu Dedeoglu, Canan Atilgan
Summary: In this study, the researchers investigated the interaction and inhibition mechanisms of a newly proposed DHFR inhibitor, 4´-deoxy methyl trimethoprim (4´-DTMP). They found that the kinetic differences in the inhibitory effects between 4´-DTMP and trimethoprim (TMP) can be attributed to the polar modification in 4´-DTMP, which induces additional interactions with the enzyme. These changes propagate through the hydrogen bond networks in the whole enzyme. The study also highlighted the importance of avoiding segmentation of the loop domain in inhibitor-bound DHFR.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Ecology
David Kneis, Claudele Lemay-St-Denis, Stella Cellier-Goetghebeur, Alan X. Elena, Thomas U. Berendonk, Joelle N. Pelletier, Stefanie Hess
Summary: In this study, shotgun metagenomics was used to estimate the abundance of dfrB gene variants in aquatic environments. The results showed that dfrB1, dfrB2, dfrB3, dfrB4, dfrB5, and dfrB7 were more prevalent in wastewater microbiomes, while dfrB9, dfrB10, and dfrB13 were more prevalent in freshwater. This suggests that natural freshwater communities serve as a major reservoir for the recently discovered dfrB gene variants.
Article
Chemistry, Medicinal
Hongyi Zhou, Hongnan Cao, Jeffrey Skolnick
Summary: In modern drug discovery, virtual ligand screening (VLS) is commonly used to reduce time and cost before experimental ligand screening. A new approach called FRAGSITE improves VLS precision and recall by integrating ligand fragment scores with global ligand similarity scores, outperforming state-of-the-art methods and showing better performance on challenging sets.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Infectious Diseases
Lachlan Jake Munro, Douglas B. Kell
Summary: Antibiotic resistance is a major global healthcare issue, and modification of membrane transporters is a key mechanism driving this resistance. This study demonstrates that transporters play a role in modulating the efficacy of almost all antimicrobial compounds tested, potentially influencing the development of antimicrobial resistance.
Article
Chemistry, Multidisciplinary
Jiahua Deng, Qiang Cui
Summary: This study analyzes the contributions of second-shell residues in an efficient enzyme and finds that they mainly impact catalytic efficiency by perturbing the apo state and substrate binding. Mutations of these residues also modulate the active site hydration level, influencing the energetics of phosphoryl transfer. These mechanistic insights can inform strategies for improving enzyme design and engineering beyond the current focus on the first coordination shell.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Bhishem Thakur, Kanika Arora, Archit Gupta, Purnananda Guptasarma
Summary: Researchers investigated whether the nucleoid-associated histone-like protein (HU) could act as a glue in biofilms, finding evidence through various experiments to support this hypothesis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Bilkis Mehrin Moni, Joanna A. Quaye, Giovanni Gadda
Summary: Enzymes require flexible regions for catalysis, and the mobile regions of enzymes include gates that regulate the passage of molecules in and out of the active site. Q80 in loop 3 of the enzyme NQO plays a mechanistically essential role in NADH binding, but does not significantly affect quinone binding and hydride transfer.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biology
Vladimir Potemkin, Maria Grishina
Summary: New approaches have been proposed to assess enzyme-ligand complementarity, taking into account hydrogens, through calculation of three-dimensional maps of electron density in receptor-ligand complexes. The study demonstrates the action of complementarity factors on complexes of human DHFR with ligands. High complementarity is ensured by the formation of effective intermolecular contacts, primarily through paired atomic-atomic interactions, while minimizing interactions of the bifurcate and more disoriented type. Additionally, an analytical docking algorithm based on the proposed receptor-ligand complementarity factors is suggested.
Article
Chemistry, Multidisciplinary
Louis Y. P. Luk, J. Javier Ruiz-Pernia, Aduragbemi S. Adesina, E. Joel Loveridge, Inaki Tunon, Vincent Moliner, Rudolf K. Allemann
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2015)
Article
Chemistry, Physical
Louis Y. P. Luk, E. Joel Loveridge, Rudolf K. Allemann
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2015)
Article
Chemistry, Multidisciplinary
J. Javier Ruiz-Pernia, Enas Behiry, Louis Y. P. Luk, E. Joel Loveridge, Inaki Tunon, Vicent Moliner, Rudolf K. Allemann
Article
Microbiology
E. Joel Loveridge, Cerith Jones, Matthew J. Bull, Suzy C. Moody, Malgorzata W. Kahl, Zainab Khan, Louis Neilson, Marina Tomeva, Sarah E. Adams, Andrew C. Wood, Daniel Rodriguez-Martin, Ingrid Pinel, Julian Parkhill, Eshwar Mahenthiralingam, John Crosby
JOURNAL OF BACTERIOLOGY
(2017)
Article
Chemistry, Multidisciplinary
Antonio Angelastro, William M. Dawson, Louis Y. P. Luk, E. Joel Loveridge, Rudolf K. Allemann
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2017)
Article
Biotechnology & Applied Microbiology
Claire M. Hull, E. Joel Loveridge, Nicola J. Rolley, Iain S. Donnison, Steven L. Kelly, Diane E. Kelly
BIOTECHNOLOGY FOR BIOFUELS
(2014)
Review
Biotechnology & Applied Microbiology
Suzy C. Moody, E. Joel Loveridge
JOURNAL OF APPLIED MICROBIOLOGY
(2014)
Article
Chemistry, Multidisciplinary
Louis Y. P. Luk, E. Joel Loveridge, Rudolf K. Allemann
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2014)
Article
Chemistry, Multidisciplinary
Louis Y. P. Luk, J. Javier Ruiz-Pernia, William M. Dawson, E. Joel Loveridge, Inaki Tunon, Vicent Moliner, Rudolf K. Allemann
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2014)
Article
Biotechnology & Applied Microbiology
Claire M. Hull, E. Joel Loveridge, Iain S. Donnison, Diane E. Kelly, Steven L. Kelly
Article
Immunology
Florian Madura, Pierre J. Rizkallah, Mateusz Legut, Christopher J. Holland, Anna Fuller, Anna Bulek, Andrea J. Schauenburg, Andrew Trimby, Jade R. Hopkins, Stephen A. Wells, Andrew Godkin, John J. Miles, Malkit Sami, Yi Li, Nathaniel Liddy, Bent K. Jakobsen, E. Joel Loveridge, David K. Cole, Andrew K. Sewell
EUROPEAN JOURNAL OF IMMUNOLOGY
(2019)
Review
Chemistry, Physical
Adam H. Day, Samuel J. Adams, Laia Gines, Oliver A. Williams, Benjamin R. G. Johnson, Ian A. Fallis, E. Joel Loveridge, Gurmit S. Bahra, Petra C. F. Oyston, Juan Manuel Herrera, Simon J. A. Pope
Review
Biotechnology & Applied Microbiology
Andrew R. Cowan, Chiara M. Costanzo, Robert Benham, E. Joel Loveridge, Suzy C. Moody
Summary: Plastics, specifically polyethylene, are prevalent as materials and environmental pollutants due to long-term mass production and inadequate waste management. Current recycling and incineration processes are not sustainable solutions for tackling plastic waste, highlighting the need for the development of new waste-management technologies. Fungal-based biodegradation, particularly in relation to polyethylene, shows promise as a potential future solution to plastic waste.
JOURNAL OF APPLIED MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Robert L. Hughes, Luke A. Johnson, Enas M. Behiry, E. Joel Loveridge, Rudolf K. Allemann
Article
Biochemistry & Molecular Biology
E. Joel Loveridge, Lukas Hroch, Robert L. Hughes, Thomas Williams, Rhidian L. Davies, Antonio Angelastro, Louis Y. P. Luk, Giovanni Maglia, Rudolf K. Allemann