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Microbiology
Manickam Yogavel, Alexandre Bougdour, Siddhartha Mishra, Nipun Malhotra, Jyoti Chhibber-Goel, Valeria J. Bellini, Karl Harlos, Benoit J. Laleu, Mohamed-Ali Hakimi, Amit J. Sharma
Summary: Researchers have discovered that a compound called PPL can bind to a protein involved in the pathogenic mechanism of the Toxoplasma parasite and kill it. Mutations in the protein structure related to PPL have been identified through genetic mutation and DNA sequencing analysis. Therefore, this study provides a method for enhancing the activity of this compound series.
Article
Biochemistry & Molecular Biology
Matteo de Rosa, Simona Nonnis, Alessandro Aliverti
Summary: The protozoan Plasmodium falciparum is the main cause of tropical malaria, with a unique organelle and redox system essential for its survival. This study identified important amino acid residues for PfFNR activity and explored covalent inhibition strategies targeting these residues.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Microbiology
Mrinalini Roy, Aadish Rawat, Sanket Kaushik, Anupam Jyoti, Vijay Kumar Srivastava
Summary: This article reviews the endogenous inhibitors of cysteine proteases in three major pathogenic parasitic protozoa. The inhibitors target proteases involved in host-parasite interactions and are also involved in other functions of the parasites. They show limited sequence homology and are linked to parasite biology and evolution.
MICROBIOLOGICAL RESEARCH
(2022)
Article
Medicine, Research & Experimental
Haiyang Yang, Xueyan Li, Gang Li, Huating Huang, Wenning Yang, Xiaoquan Jiang, Muli Sen, Jingjing Liu, Yang Liu, Yanli Pan, Guopeng Wang
Summary: This study emphasizes the importance of accurate quantitative determination of affinity and binding kinetics for tight binding inhibition. Recommendations on experimental design and mathematical calculation approaches are provided to evaluate affinity and BK parameters for inhibitors against xanthine oxidase. Significant differences in results and the influence of different data analytical methods on enzyme engagement in human are discussed.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Medicinal
Carlos Moreno-Yruela, Christian A. Olsen
Summary: This study highlights the importance of thorough kinetic investigation in the development of selective HDAC probes. Potent inhibitors of HDACs 1-3 often display slow-binding kinetics, and this study compares the potencies and selectivities of slow-binding inhibitors measured by discontinuous and continuous assays.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Analytical
Shuai Yan, Dongqing Zhao, Chunqing Wang, Hao Wang, Xinyu Guan, Yan Gao, Xiangyang Zhang, Ning Zhang, Ruibing Chen
Summary: This study established an analytical strategy to characterize RNA-binding proteins from different subcellular regions, identifying a large number of known and novel RBPs and cataloging their subcellular localizations. The observation of metabolic enzymes as RBPs highlights the potential role of RNA-binding in regulating cellular metabolism.
ANALYTICA CHIMICA ACTA
(2021)
Article
Biochemistry & Molecular Biology
Ante Bubic, Marta Narczyk, Ana Petek, Marta Ilona Wojtys, Weronika Maksymiuk, Beata Wielgus-Kutrowska, Maria Winiewska-Szajewska, Tea Pavkov-Keller, Branimir Bertosa, Zoran Stefanic, Marija Luic, Agnieszka Bzowska, Ivana Lescic Asler
Summary: This study characterizes the His6-tagged adenylosuccinate synthetase (AdSS) from Helicobacter pylori and identifies the interactions crucial for ligand binding and enzyme activity. Experimental and molecular dynamics simulations show the importance of the hydrogen bond Arg135-IMP for enzyme dimerization and active site formation. The findings provide a basis for designing new AdSS inhibitors as potential drugs against H. pylori.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Immunology
Katja Mueller, Olivier Silvie, Hans-Joachim Mollenkopf, Kai Matuschewski
Summary: The deletion of the UIS12 gene in Plasmodium parasites results in a decrease in gametocyte formation, oocyst development, and ultimately, the production of salivary gland sporozoites in Anopheles mosquitoes. Transcript profiling shows a reduction in specific protein coding mRNAs in mutant parasites, indicating the diverse regulatory roles of UIS12 in gene expression during blood infection.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Stephane Hausmann, Johan Geiser, Martina Valentini
Summary: RNA helicases, including microbial RNA helicases, can be potential drug targets. In this study, the researchers screened a library of molecules and identified a potent inhibitor, CSB, for RhlE2 RNA helicase. They also investigated the inhibitory mechanism and found other diazo dyes that affect RhlE homologs differently. This research provides valuable insights for future drug development.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Neurosciences
Rajeshwari Chellappan, Abhishek Guha, Ying Si, Thaddaeus Kwan, Louis B. Nabors, Natalia Filippova, Xiuhua Yang, Anish S. Myneni, Shriya Meesala, Ashley S. Harms, Peter H. King
Summary: Glial activation with the production of pro-inflammatory mediators is driven by HuR, an RNA regulator that plays a critical role in regulating inflammatory cytokine production in glia. The development of a small molecule inhibitor, SRI-42127, which blocks HuR's translocation, has shown promising effects in suppressing the production of pro-inflammatory mediators and microglial activation, indicating the potential for treating neurological diseases driven by this activation.
Article
Neurosciences
Mohadeseh Kalari, Zeinab Abbasi, Marzieh Dehghan Shasaltaneh, Ali Khaleghian, Zahra Moosavi-Nejad
Summary: This study investigated the inhibitory function of a synthetic complex containing cobalt (SC) on acetylcholinesterase (AChE) activity for the first time. The results showed that SC had a stronger inhibitory effect on AChE compared to galantamine, and this effect was related to the changes in the protein structure of AChE.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Agriculture, Multidisciplinary
Qiang Lu, Daopeng Tan, Yifei Xu, Meigui Liu, Yuqi He, Cailan Li
Summary: Nitidine chloride is a non-competitive inhibitor of urease that targets the active site thiol group. It exhibits characteristics of concentration dependence, reversibility, and slow binding, making it a promising novel urease suppressant.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Microbiology
Yogavel Manickam, Nipun Malhotra, Siddhartha Mishra, Palak Babbar, Abhishek Dusane, Benoit Laleu, Valeria Bellini, Mohamed-Ali Hakimi, Alexandre Bougdour, Amit Sharma
Summary: This study describes the simultaneous targeting of multiple binding sites of the enzyme prolyl-tRNA synthetase (PRS) in Toxoplasma gondii using two potent inhibitors, halofuginone (HFG) and L95. The inhibitors form a ternary complex with the enzyme, inhibiting its activity and showing additive effects in parasite inhibition assays. This novel approach validates the potential of targeting multiple pockets to inhibit druggable proteins, providing a structural framework for further drug development.
Article
Biochemistry & Molecular Biology
Jakob Trendel, Etienne Boileau, Marco Jochem, Christoph Dieterich, Jeroen Krijgsveld
Summary: Post-transcriptional gene regulation is achieved through the interaction between the transcriptome and RNA-binding proteins, and can dynamically respond to changes in cellular conditions. A method called PEPseq, using RNA sequencing, is established to monitor protein occupancy in a transcriptome-wide manner. It allows the investigation of changes in protein occupancy during translational stress and reveals an increase in protein interactions in specific mRNA coding regions. The PEPseq method serves as an unbiased discovery platform for studying post-transcriptional regulation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Immunology
Mamoru Niikura, Toshiyuki Fukutomi, Jiro Mitobe, Fumie Kobayashi
Summary: This study revealed that NAB2 and SR1 play essential roles in the asexual development of malaria parasites, while GBP2 is involved in male and female gametocyte production. The cellular localization and protein interactions of GBP2 and NAB2 suggest a conserved mechanism used by malaria parasites.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)