Article
Chemistry, Multidisciplinary
Aaron T. Balana, Paul M. Levine, Timothy W. Craven, Somnath Mukherjee, Nichole J. Pedowitz, Stuart P. Moon, Terry T. Takahashi, Christian F. W. Becker, David Baker, Matthew R. Pratt
Summary: The study found that O-GlcNAc can activate the anti-amyloid activity of certain small heat shock proteins, inhibiting protein aggregation. Although O-GlcNAc levels are globally reduced in Alzheimer's disease brains, the modification of relevant small heat shock proteins is either maintained or increased, suggesting a mechanism to maintain these potentially protective O-GlcNAc modifications.
Article
Chemistry, Multidisciplinary
Anjali Dixit, Ankan Chakraborty, Jyoti Rani Nath, Pramit K. Chowdhury, Bishwajit Kundu
Summary: Optineurin (OPTN) is a multifunctional protein associated with primary open-angle glaucoma and amyotrophic lateral sclerosis. OPTN is present in ocular tissues and has the ability to form higher-order multimers upon heating. It also exhibits chaperone-like function and can restore its native structure after denaturation.
Review
Environmental Sciences
Jieting Wu, Tian Gao, Jianing Hu, Lei Zhao, Chang Yu, Fang Ma
Summary: Plants respond to stresses by expressing sHSPs, which play significant roles in inhibiting protein aggregation, protecting cell integrity, and improving resistance. This review systematically summarizes the classification, structure, and functions of sHSPs in plants, with a focus on their roles in promoting fruit ripening and plant growth, protecting photosynthesis, and improving antioxidant activity. The production and regulatory mechanisms of sHSPs are also discussed, along with recent efforts to constitutively express sHSPs in transgenic plants to enhance stress resistance.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Review
Cell Biology
Ying Liu, Lin Zhou, Yunfei Xu, Kexin Li, Yao Zhao, Haoduo Qiao, Qing Xu, Jie Zhao
Summary: This study systematically summarizes the roles of heat shock proteins in the occurrence of ferroptosis and predicts the possible mechanisms of different families of heat shock proteins in the development of ferroptosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Chemistry, Medicinal
Giusy Tassone, Marco Mazzorana, Cecilia Pozzi
Summary: Protozoan parasites are responsible for harmful diseases in humans, and new specific drug therapies are urgently needed. HSP90 plays a key role in parasite survival, with the N-terminal domain being a crucial target for inhibitor development.
Article
Biotechnology & Applied Microbiology
Zhanwu Yang, Hui Du, Xinzhu Xing, Wenlong Li, Youbin Kong, Xihuan Li, Caiying Zhang
Summary: This study identified an important sHSP protein GmHSP17.9 in soybean nodules, revealing its significant role in nodule development and nitrogen fixation. GmHSP17.9 interacts with GmNOD100, influencing the function of soybean nodules.
PLANT BIOTECHNOLOGY JOURNAL
(2022)
Article
Cell & Tissue Engineering
Ju-Fang Liu, Po-Chun Chen, Thai-Yen Ling, Chun-Han Hou
Summary: This study demonstrates that heat shock induces the expression of HSPs in hPDMCs through the activation of ROS, p38 MAPK, Akt signaling, and HSF1, which plays a protective role.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Cell Biology
Philip Kaenel, Gundula A. Noll, Katrin Schroedter, Elke Naffin, Julia Kronenberg, Franziska Busswinkel, Richard M. Twyman, Christian Klaembt, Dirk Pruefer
Summary: Proteostasis, the balance of protein synthesis, trafficking, and degradation, plays a crucial role in cellular function and aging. The authors found that ectopic expression of the tobacco PEBP NtFT4 in Drosophila melanogaster extended lifespan and improved locomotor decline associated with aging. NtFT4 influenced proteome maintenance through physical interactions and transcriptional regulation, including the prolonged expression of HSP26 gene, which maintained protein integrity and contributed to longevity.
Article
Biochemistry & Molecular Biology
Digvijay Singh, Prajna Tripathi, Rahul Sharma, Sonam Grover, Janendra K. Batra
Summary: The N-terminal domain of Mtb ClpB plays a crucial role in the interaction with its co-partners and in the prevention of aggregation of proteins. The substrate binding pocket identified in this study, comprising of nine amino acid residues forming an alpha-helix, is important for the function of ClpB in repairing and resolubilizing aggregated proteins.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Joung Hun Park, Eun Seon Lee, Young Jun Jung
Summary: The DNA-binding protein from starved cells, known as DPS, acts as a crucial factor in protecting E. coli from external stresses. Under heat shock conditions, DPS protein functions as a novel molecular chaperone, preventing substrate proteins from aggregation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Microbiology
Paolo Costa, Giulia Usai, Angela Re, Marcello Manfredi, Giuseppe Mannino, Cinzia Margherita Bertea, Enrica Pessione, Roberto Mazzoli
Summary: Comparative gel-free proteomics analysis of Clostridium cellulovorans exposed to butanol revealed modulation of protein biosynthesis, up-regulation of ATPases, and rearrangement of cell envelope, suggesting potential gene targets for metabolic engineering strategies aimed at improving butanol tolerance in this microbial strain.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
V. Sudhakar Reddy, S. Pandarinath, M. Archana, G. Bhanuprakash Reddy
Summary: Chronic hyperglycemia induces differential responses of sHsps by altering their expression, solubility, interaction, and roles in apoptosis in neuronal cells, potentially contributing to cell death.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Neurosciences
Gouri Chopra, Shabnam Shabir, Sumaira Yousuf, Simran Kauts, Shahnawaz A. Bhat, Ashiq H. Mir, Mahendra P. Singh
Summary: Neurodegenerative diseases are a cluster of diseases characterized by progressive neuronal loss and protein misfolding and aggregation. Recent studies have found that these misfolded proteins can translocate from one neuron to another, which has implications for understanding the onset and progression of the diseases and developing innovative therapies and diagnostics.
MOLECULAR NEUROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kevin Reinle, Axel Mogk, Bernd Bukau
Summary: The protein quality control system maintains protein homeostasis through substrate degradation, refolding, and sequestration activities, in which small heat shock proteins play a crucial role and adapt to different tasks and stress conditions.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Bianca Nitzsche, Michael Hoepfner, Bernhard Biersack
Summary: Heat shock protein 70 (Hsp70) and its interaction with Hsp90 play a significant role in cancer diseases. The Hsp70-Hsp40 axis, formed by the connection between Hsp70 and a smaller heat shock protein Hsp40, is a suitable target for designing anticancer drugs. This review discusses the current state and recent developments in the field of (semi-)synthetic small molecule inhibitors targeting Hsp70 and Hsp40, as well as their potential in medicinal chemistry and anticancer therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Dries De Ruysscher, Luping Pang, Charles-Alexandre Mattelaer, Manesh Nautiyal, Steff De Graef, Jef Rozenski, Sergei Strelkov, Eveline Lescrinier, Stephen D. Weeks, Arthur Van Aerschot
BIOORGANIC & MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Vladislav M. Shatov, Sergei V. Strelkov, Nikolai B. Gusev
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cell Biology
Giel Stalmans, Anastasia Lilina, Pieter-Jan Vermeire, Jan Fiala, Petr Novak, Sergei Strelkov
Article
Biochemistry & Molecular Biology
Machteld Sillen, Stephen D. Weeks, Sergei Strelkov, Paul J. Declerck
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Chemistry, Medicinal
Dries De Ruysscher, Luping Pang, Stijn M. G. Lenders, Davie Cappoen, Paul Cos, Jef Rozenski, Sergei Strelkov, Stephen D. Weeks, Arthur Van Aerschot
Summary: LeuRS is a clinically validated target for antimicrobial development, and bi-substrate inhibitors have shown potent inhibitory activity against bacterial LeuRS. The results of the study could serve as a suitable starting point for further antibiotic development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Luping Pang, Stephen D. Weeks, Arthur Van Aerschot
Summary: Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in all three kingdoms of life, and have been recognized as suitable targets for small molecule anti-infectives. This review discusses the catalytic activities of aaRSs, inhibitory mechanisms, and species-selectivity determinants of reported inhibitors. The structural perspective highlights opportunities for further exploration of the aaRS enzyme family as antimicrobial targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Madeline Loffredo, Hector Lucero, Da-Yuan Chen, Aoife O'Connell, Simon Bergqvist, Ahmad Munawar, Asanga Bandara, Steff De Graef, Stephen D. Weeks, Florian Douam, Mohsan Saeed, Ali H. Munawar
Summary: Multiple studies have suggested the repositioning of famotidine, an approved drug, for the treatment of COVID-19 due to the lack of specific antiviral drugs for the coronavirus. While potential molecular targets have been proposed, experimental results show that famotidine does not directly inhibit SARS-CoV-2 replication. Further research is needed to explore the molecular mechanism of famotidine in the context of COVID-19.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Luping Pang, Stephen D. Weeks, Martin Juhas, Sergei Strelkov, Jan Zitko, Arthur Van Aerschot
Summary: HcProRS catalyzes prolyl-tRNA synthesis and inhibiting its activity may benefit treatment of fibrosis, autoimmune diseases, and cancer. Recent research identified potential novel HcProRS inhibitors from a pyrazinamide-based compound library, showing promise for repurposing old drug candidates for HcProRS-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Pieter-Jan Vermeire, Giel Stalmans, Anastasia Lilina, Jan Fiala, Petr Novak, Harald Herrmann, Sergei Strelkov
Summary: IFs play a crucial role in normal cell physiology and are linked to numerous diseases, highlighting the importance of understanding their molecular structure. While progress has been made in studying the IF structure, many mysteries and challenges remain. In addition to X-ray crystallography, chemical cross-linking and cryoelectron microscopy are expected to lead to major advancements in the field in the near future.
Article
Biology
Luping Pang, Vladimir Zanki, Sergei Strelkov, Arthur Van Aerschot, Ita Gruic-Sovulj, Stephen D. Weeks
Summary: Crystal structures of leucyl-tRNA synthetase in Neisseria gonorrhoeae reveal conformational changes and a peptide-plane flip in the active site that correlate with catalytic steps. These structural alterations have a significant impact on the enzyme's activity.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Luping Pang, Stijn Lenders, Evgenii M. Osipov, Stephen D. Weeks, Jef Rozenski, Tatiana Piller, Davie Cappoen, Sergei V. Strelkov, Arthur Van Aerschot
Summary: Mycothiol (MSH) is the major cellular thiol in Mycobacterium tuberculosis (Mtb) and plays a crucial role in the resistance to antibiotics and oxidative stresses. This study focused on MshC, an enzyme involved in the synthesis of MSH, and synthesized five new compounds with potential inhibitory effects on MshC. The compounds showed strong binding affinity with MshC, but did not suppress the growth of Mtb culture, possibly due to inadequate cellular uptake.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Evgenii M. Osipov, Ali H. Munawar, Steven Beelen, Daren Fearon, Alice Douangamath, Conor Wild, Stephen D. Weeks, Arthur Van Aerschot, Frank von Delft, Sergei Strelkov
Summary: Polyomaviruses, including BK polyomavirus and Merkel cell polyomavirus, are human pathogens for which no specific drugs are available. In this study, we focused on the structural protein VP1 of BK polyomavirus and used high-throughput screening to identify drug-like fragments that bind to truncated VP1 pentamers. We found a total of 144 binding hits, which cluster in six surface pockets. These findings provide a foundation for rational drug design targeting polyomavirus capsid assembly.
RSC CHEMICAL BIOLOGY
(2022)