Article
Biochemistry & Molecular Biology
Christoph Grininger, Mario Leypold, Philipp Aschauer, Tea Pavkov-Keller, Lina Riegler-Berket, Rolf Breinbauer, Monika Oberer
Summary: The study uncovered new insights into the structural changes of the monoacylglycerol lipase of Mycobacterium tuberculosis, highlighting its importance as a potential therapeutic target.
Article
Chemistry, Multidisciplinary
Yohei Katsuyama, Kaoru Sone, Ayaka Harada, Seiji Kawai, Naoki Urano, Naruhiko Adachi, Toshio Moriya, Masato Kawasaki, Kazuo Shin-ya, Toshiya Senda, Yasuo Ohnishi
Summary: The study determined the structure of FmoA3 using X-ray crystallography and cryogenic electron microscopy, revealing the accommodation of alpha-methyl-l-serine in the active site. The Cy domains of FmoA2 and FmoA3 catalyze different reactions, with the Cy domain of FmoA3 potentially losing its donor PCP binding activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Ki-Hwa Kim, Chang Woo Lee, Bashu Dev Pardhe, Jisub Hwang, Hackwon Do, Yung Mi Lee, Jun Hyuck Lee, Tae-Jin Oh
Summary: 7 alpha-Hydroxysteroid dehydrogenase (7 alpha-HSDH) plays a role in catalyzing the dehydrogenation of steroid substrates at the 7 alpha position. Structural studies reveal significant conformational changes in the apo form of 7 alpha-HSDH, with only the ternary complex structure showing a fully closed conformation. The transition from open to closed conformation is essential for catalytic activity, positioning important residues for catalysis.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Article
Agriculture, Multidisciplinary
Samantha L. Griffin, Jonathan R. Chekan, Justin M. Lira, Andrew E. Robinson, Carla N. Yerkes, Daniel L. Siehl, Terry R. Wright, Satish K. Nair, Robert M. Cicchillo
Summary: The newly discovered EPSPS from Streptomyces sviceus represents a distinct new class (Class IV) of EPSPS enzymes that display intrinsic tolerance to high concentrations of glyphosate. By transforming dgt-28 epsps gene into stable plants, it provides robust (≥ 4x field rates) herbicide tolerance and has utility in weed-control systems comparable to commercialized events.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Chemistry, Physical
Qi Han, Kate M. Smith, Connie Darmanin, Timothy M. Ryan, Calum J. Drummond, Tamar L. Greaves
Summary: This study investigates the conformational changes of lysozyme in the presence of ionic liquids using a combination of spectroscopic techniques, small angle X-ray scattering, and X-ray crystallography. The results show that the secondary structure of lysozyme remains stable while the tertiary structure, particularly the loop regions, are sensitive to the concentration and type of ionic liquids.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Qingjie Xiao, Ting Xue, Wen Shuai, Chengyong Wu, Zhixiong Zhang, Ting Zhang, Shaoxue Zeng, Bo Sun, Yuxi Wang
Summary: Crystal structures of three taxane-site inhibitors, Ixabepilone, Epothilone B, and Epothilone D, were reported, showing similar binding modes to promote tubulin polymerization. Through virtual screening, novel taxane-site inhibitors with simpler chemical structures were identified, and derivatives with higher binding affinity to tubulin were designed and developed.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Agronomy
Pamela Carvalho-Moore, Jason K. Norsworthy, Fidel Gonzalez-Torralva, Jeong-In Hwang, Jinesh D. Patel, L. Tom Barber, Thomas R. Butts, J. Scott McElroy
Summary: This study identified glufosinate resistance in Palmer amaranth from Arkansas, USA. Gene amplification and increased expression of the chloroplastic glutamine synthetase enzyme were found to be the mechanisms conferring glufosinate resistance in this species.
Review
Pharmacology & Pharmacy
Md. Moinul, Samima Khatun, Sk. Abdul Amin, Tarun Jha, Shovanlal Gayen
Summary: This review discusses the application of fragment-based drug design in cancer treatment, as well as the design strategies for different targets, providing insights for finding suitable lead compounds through fragment-based design in high throughput screening.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Jonathan Cook, Tyler C. Baverstock, Martin B. L. McAndrew, David I. Roper, Phillip J. Stansfeld, Allister Crow
Summary: AmiA and AmiB are enzymes from Escherichia coli that break the peptidoglycan layer and maintain cell integrity. Their activity is controlled by interactions with the FtsEX-EnvC complex. The structures of AmiA and AmiB in different states were determined, revealing the conformational changes required for activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Davide Capelli, Giulia Cazzaniga, Matteo Mori, Antonio Laghezza, Fulvio Loiodice, Martina Quaglia, Elisa Negro, Fiorella Meneghetti, Stefania Villa, Roberta Montanari
Summary: PPAR gamma is a key target for the treatment of type 2 diabetes and metabolic syndrome. To avoid adverse effects, a new opportunity is the development of molecules that inhibit PPAR gamma phosphorylation by CDK5. The study reports the identification of new PPAR gamma binders that exhibit a non-agonist profile and prevent PPAR gamma phosphorylation by stabilizing the protein and weakly inhibiting CDK5.
Article
Biochemistry & Molecular Biology
Camila Campos-Escamilla, Dritan Siliqi, Luis A. Gonzalez-Ramirez, Carmen Lopez-Sanchez, Jose Antonio Gavira, Abel Moreno
Summary: The conformational changes of iron-free and iron-loaded transferrin at different pH values were studied using Macromolecular X-ray Crystallography and Small Angle X-ray Scattering techniques. While apo-Tf remained mostly globular in solution, holo-Tf showed a more elongated and flexible shape with co-existing closed, partially open, and open conformations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Jonathan Blachier, Aurore Cleret, Nathalie Guerin, Clara Gil, Jean-Marc Fanjat, Florian Tavernier, Laura Vidault, Fanny Gallix, Nicolas Rama, Rodrigue Rossignol, Diana Piedrahita, Aurely Andrivon, Marie Chalons-Cottavoz, Karine Aguera, Fabien Gay, Francoise Horand, Bastien Laperrousaz
Summary: L-Asparaginase is critical in ALL therapy, but its efficacy in solid tumors is unclear due to ASNS expression. However, it has a glutaminase activity in pancreatic cancer. By studying L-Asparaginase-resistant pancreatic cancer cells, we identified GS as a marker of resistance and its correlation with L-Asparaginase efficacy in various cancer cell lines. Furthermore, GS inhibition prevents cancer cell adaptation to L-Asparaginase-induced glutamine starvation, suggesting potential drug combinations to overcome resistance.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Chemistry, Medicinal
Martyn Frederickson, Irwin R. Selvam, Dimitrios Evangelopoulos, Kirsty J. McLean, Mona M. Katariya, Richard B. Tunnicliffe, Bethany Campbell, Madeline E. Kavanagh, Sitthivut Charoensutthivarakul, Richard T. Blankley, Colin W. Levy, Luiz Pedro S. de Carvalho, David Leys, Andrew W. Munro, Anthony G. Coyne, Chris Abell
Summary: A novel strategy combining X-ray crystallographic screening with phenotypic screening is described for hit generation against promising tuberculosis (TB) targets. This method provides validation of target engagement and determination of in vitro activity. The utility of this approach is demonstrated through the screening against CYP121A1, a validated drug discovery target for TB. Several compounds showed promising activity against Mycobacterium tuberculosis strain H37Rv, and structure-based design resulted in analogues with pan-assay activity. This study highlights the importance of developing new drugs for combating drug resistance in TB.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Crystallography
Sehyeok Im, Hackwon Do, Jisub Hwang, Youn-Soo Shim, Jun Hyuck Lee
Summary: The crystal structure of the FolD enzyme from Porphyromonas gingivalis was determined, revealing its role in the chemical modification of tetrahydrofolate. Comparison with previously known FolD enzymes showed differences in substrate-binding site residue composition.
Article
Chemistry, Medicinal
Shan Yan, Changxing Qi, Wei Song, Qianqian Xu, Lianghu Gu, Weiguang Sun, Yonghui Zhang
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal digestive system cancer. This study discovered three butyrolactone derivatives from a marine-derived fungus Aspergillus terreus, with one compound AH showing strong in vitro inhibitory activity and promising in vivo antitumor effects in a xenograft model. The findings suggest that AH could be a potential lead compound for developing anti-PDAC agents.
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)