Article
Biochemistry & Molecular Biology
Sana Tanweer, Salma Jamal, Seema Mehra, Najumu Saqib, Faraz Ahmad, Faizan, Abhinav Grover, Sonam Grover
Summary: Tuberculosis is a major cause of death worldwide, with drug-resistant strains posing challenges for clinicians and public health centers. Individuals with compromised immune systems, HIV infection, or diabetes have a high risk of death.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Immunology
Yuki Arimura, Yusuke Minato, Takayuki Wada, Masaaki Nakayama, Ayako Ryumon, Nao Hirata, Chie Nakajima, Yasuhiko Suzuki, Manabu Ato, Kazuo Kobayashi, Naoko Ohara, Seiji Iida, Naoya Ohara
Summary: The study assessed the essentiality of thyX in Mycobacterium bovis BCG strains using CRISPR interference and found that thyX is not essential in a specific genetic background. A thyX deletion mutant strain was successfully constructed from that strain, confirming the non-essentiality of thyX.
MICROBIOLOGY AND IMMUNOLOGY
(2022)
Review
Chemistry, Medicinal
Milan Urban, Veronika Slachtova, Lucie Brulikova
Summary: Mycobacterial energy metabolism, particularly the oxidative phosphorylation pathway, has become increasingly important as a molecular target for the development of new anti-TB drugs. Small organic molecules targeting this pathway have shown promising activity against latent and resistant TB strains, with FDA-approved inhibitors confirming the value of targeting mycobacterial energy metabolism.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Manuel Gehl, Ulrike Demmer, Ulrich Ermler, Seigo Shima
Summary: FAD-independent methylene-tetrahydrofolate reductase (Mfr) catalyzes the reduction of methylene-H4F to methyl-H4F with NADH as hydride donor. Mfr is essential for the growth of Mycobacterium tuberculosis, making it a potential target for antimycobacterial drug design.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Chemistry, Medicinal
Hamish S. S. Sutherland, Guo-Liang Lu, Amy S. T. G. Tong, Daniel M. Conole, Scott G. U. Franzblau, Anna B. Upton, Manisha U. D. Lotlikar, Christopher B. J. Cooper, Brian D. A. Palmer, Peter J. Choi, William A. Denny
Summary: This study reports tetrahydronaphthalene amides (THNAs) as a new class of ATP synthase inhibitors that effectively inhibit the growth of Mycobacterium tuberculosis (M.tb). The design, synthesis, and structure-activity relationship studies of THNA analogues were conducted, and several compounds with potent in vitro M.tb growth inhibition were identified. Pharmacokinetic and off-target profiling studies were also performed to evaluate the potential of these THNAs as therapeutic options for TB.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Nicolas G. Biteau, Vincent Roy, Jean-Christophe Lambry, Hubert F. Becker, Hannu Myllykallio, Luigi A. Agrofoglio
Summary: Researchers discovered a new class of thymidylate synthase for developing new antibacterial agents against multiresistant pathogens. They developed a new class of ANPs based on natural cofactors, with some compounds showing weak inhibitory effects in experiments.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Jayanthi J. Joseph, Amy Leestemaker-Palmer, Soheila Kazemi, Lia Danelishvili, Luiz E. Bermudez
Summary: This study investigated the role of multinucleated giant cells (MGCs) in Mycobacterium avium infection. The results showed that MGCs can uptake M. avium and the escaped bacteria exhibit a highly invasive phenotype. Autophagy markers are upregulated in infected MGCs, and inhibition of autophagy reduces M. avium survival. Depletion of host cholesterol and sphingomyelin also decreases M. avium survival in MGCs.
CELLULAR MICROBIOLOGY
(2023)
Review
Immunology
Reshma S. Rudraraju, Samer S. Daher, Ricardo Gallardo-Macias, Xin Wang, Matthew B. Neiditch, Joel S. Freundlich
Summary: This review summarizes the current research progress on the druggable target KasA in Mycobacterium tuberculosis, focusing on structure-based design methods using X-ray crystal structures. The discussed inhibitor classes and their interactions with KasA provide insights into the development of new KasA inhibitors for studying the basic biology of M. tuberculosis and combating drug-sensitive and drug-resistant infections.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Chemistry, Medicinal
Sandra Valeria Vassiliades, Lara Gimenez Borges, Jeanine Giarolla, Roberto Parise-Filho
Summary: The folate metabolic cycle is a crucial process for cellular homeostasis and replication control. Recent studies have expanded the potential targets for new antituberculosis drugs by exploring enzymes within this cycle. This review summarizes the history of these enzymes and presents synthetic strategies for the most promising inhibitors.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2023)
Review
Microbiology
Liudmila A. Alexandrova, Anastasia L. Khandazhinskaya, Elena S. Matyugina, Dmitriy A. Makarov, Sergey N. Kochetkov
Summary: Tuberculosis is the oldest human infection disease, and a significant number of the world's population is currently infected with Mycobacterium tuberculosis. Despite a decrease in mortality, the emergence of multidrug-resistant strains has created an urgent need for new anti-TB drugs. Nucleoside analogues have shown antimycobacterial activity, but no clinically used drugs based on them exist yet.
Article
Biochemistry & Molecular Biology
Benjamin T. Grosse-Siestrup, Tuhina Gupta, Shelly Helms, Samantha L. Tucker, Martin I. Voskuil, Frederick D. Quinn, Russell K. Karls
Summary: Sigma factor C (SigC) plays a role in preventing copper starvation in Mycobacterium tuberculosis and regulates the expression of copper-related genes. Deletion of sigC leads to growth defects in a copper-deficient environment and differential expression of 40 genes, including those related to nonribosomal peptide synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Bruno Rampanelli Dahmer, Eduardo Miranda Ethur, Luis Fernando Saraiva Macedo Timmers
Summary: Tuberculosis is a highly infectious disease caused by Mycobacterium tuberculosis. The enzyme MtEPSPS is an essential target for developing new drugs for TB treatment. This study identified potential drugs through molecular docking and molecular dynamics simulations, including approved drugs like Conivaptan and Ribavirin monophosphate.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2023)
Article
Biochemistry & Molecular Biology
Xiao Wang, Wenting Zhao, Bin Wang, Wei Ding, Hao Guo, Hongyi Zhao, Jianzhou Meng, Sihan Liu, Yu Lu, Yishuang Liu, Dongfeng Zhang
Summary: The study highlights the importance of Pks13 as a drug target for tuberculosis treatment, and identifies novel chemotype inhibitors through a structure-guided approach. The results show that compounds targeting Pks13 have potential as effective antituberculosis drugs, paving the way for further development in this field.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Medha, Priyanka, Parul Bhatt, Sadhna Sharma, Monika Sharma
Summary: This study investigates the role of the unique C-terminal of Mycobacterium tuberculosis's (Mtb) PE6/Rv0335c protein in causing host mitochondrial perturbations and apoptosis. The experiments confirm that the deletion of the C-terminal domain significantly reduces mitochondrial perturbations and apoptosis, while not affecting the protein's localization to mitochondria. Additionally, the study shows that the protein increases intracellular calcium influx, with the C-terminal deletion having minimal effect on calcium influx. These findings suggest that Rv0335c may mimic eukaryotic Bcl2 proteins, leading to host mitochondrial perturbations and apoptosis.
Article
Multidisciplinary Sciences
Nicole C. Cardoso, Andrea O. Papadopoulos, Bavesh D. Kana
Summary: The study identified the functional roles of different nitrate reductase genes in Mycobacterium smegmatis, with only MSMEG_4206 playing a significant role in nitrate assimilation.
Article
Biochemistry & Molecular Biology
Sonoko Ishino, Stephane Skouloubris, Hanae Kudo, Caroline I'Hermitte-Stead, Asmae Es-Sadik, Jean-Christophe Lambry, Yoshizumi Ishino, Hannu Myllykallio
NUCLEIC ACIDS RESEARCH
(2018)
Review
Microbiology
Hannu Myllykallio, Pierre Sournia, Alice Heliou, Ursula Liebl
FRONTIERS IN MICROBIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Floriane Delpech, Yoann Collien, Pierre Mahou, Emmanuel Beaurepaire, Hannu Myllykallio, Roxane Lestini
NUCLEIC ACIDS RESEARCH
(2018)
Review
Pharmacology & Pharmacy
Alexey Aleksandrov, Hannu Myllykallio
EXPERT OPINION ON DRUG DISCOVERY
(2019)
Article
Multidisciplinary Sciences
Andreea Sodolescu, Cyril Dian, Laurent Terradot, Latifa Bouzhir-Sima, Roxane Lestini, Hannu Myllykallio, Stephane Skouloubris, Ursula Liebl
Article
Chemistry, Medicinal
Jakub Modranka, Jiahong Li, Anastasia Parchina, Michiel Vanmeert, Shrinivas Dumbre, Mayla Salman, Hannu Myllykallio, Hubert F. Becker, Roeland Vanhoutte, Lia Margamuljana, Hoai Nguyen, Rania Abu El-Asrar, Jef Rozenski, Piet Herdewijn, Steven De Jonghe, Eveline Lescrinier
Review
Biochemistry & Molecular Biology
Hubert F. Becker, Caroline L'Hermitte-Stead, Hannu Myllykallio
Article
Biochemistry & Molecular Biology
Cory J. Smith, Oscar Castanon, Khaled Said, Verena Volf, Parastoo Khoshakhlagh, Amanda Hornick, Raphael Ferreira, Chun-Ting Wu, Marc Guell, Shilpa Garg, Alex H. M. Ng, Hannu Myllykallio, George M. Church
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Vaclav Brazda, Yu Luo, Martin Bartas, Patrik Kaura, Otilia Porubiakova, Jiri Stastny, Petr Pecinka, Daniela Verga, Violette Da Cunha, Tomio S. Takahashi, Patrick Forterre, Hannu Myllykallio, Miroslav Fojta, Jean-Louis Mergny
Article
Biochemistry & Molecular Biology
Anastasia Croitoru, Morgan Babin, Hannu Myllykallio, Muriel Gondry, Alexey Aleksandrov
Summary: The study investigates the interaction between CDPS and tRNA substrate using AlbC as a model, revealing significant contributions of AlbC alpha-helix residues to tRNA binding. The simulation results explain the biochemical data well and suggest that tRNAs of the first and second substrates interact with AlbC in a similar manner. The mechanism of protein:tRNA interaction is expected to be relevant to a wide range of proteins based on the high degree of sequence and structural similarity among CDPS NYH protein subfamily members.
Article
Biophysics
Hannu Myllykallio, Hubert F. Becker, Alexey Aleksandrov
BIOPHYSICAL JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Bo Zhuang, Lipsa Nag, Pierre Sournia, Anastasia Croitoru, Rivo Ramodiharilafy, Jean-Christophe Lambry, Hannu Myllykallio, Alexey Aleksandrov, Ursula Liebl, Marten H. Vos
Summary: Quenching of flavin fluorescence by electron transfer from neighboring aromatic residues plays a significant role in flavoproteins, and can be used as a probe for the active site configuration and dynamics. Modified amino acid residues in variants can lead to changes in the temporal characteristics, indicating heterogeneous configurations of electron donor-acceptor pairs.
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Nicolas G. Biteau, Vincent Roy, Cyril Nicolas, Hubert F. Becker, Jean-Christophe Lambry, Hannu Myllykallio, Luigi A. Agrofoglio
Summary: The newly discovered FDTS is considered an attractive target for antibacterial agents against multi-resistant pathogens. A novel series of pyrido[1,2-e]purine-2,4(1H,3H)-dione analogues were synthesized and their structure-activity relationships studied, with compound 23a showing the highest inhibition.
Article
Multidisciplinary Sciences
Jonathan Filee, Hubert f F. Becker, Lucille Mellottee, Rima Zein Eddine, Zhihui Li, Wenlu Yin, Jean-Christophe Lambry, Ursula Liebl, Hannu Myllykallio
Summary: Asgard archaea are the closest known relatives of eukaryotes. The study suggests that eukaryotic and Asgard thymidylate synthases may have a bacterial origin, and lateral transfer of bacterial genes has shaped the metabolism of Asgard archaea. The capacity of eukaryotic cells to duplicate their genetic material is a combination of archaeal and bacterial characteristics, and recent prevalent lateral gene transfer from bacteria has influenced the metabolism of Asgard archaea.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Sakina Khallef, Roxane Lestini, Hannu Myllykallio, Karim Houali
CELLULAR AND MOLECULAR BIOLOGY
(2018)