Article
Biochemistry & Molecular Biology
Alan Fecchio, Henrique Batalha-Filho, Janice H. Dispoto, Jeffrey A. Bell, Jason D. Weckstein
Summary: Amazonia serves as the main source of diversity for haemosporidian parasites in South America, but our understanding of their biogeographical processes and contributions from different areas of endemism is incomplete. This study investigates the spatiotemporal evolution of Plasmodium and Parahaemoproteus parasites and finds that dispersal is the main driver of Plasmodium diversification, while duplication is more frequent in Parahaemoproteus. The results show that the Inambari area is the primary source of Plasmodium diversity on Marajó Island, but the island receives more Parahaemoproteus lineages from Cerrado habitats than any Amazonian area. The unique dispersal patterns and host-shifting ability of each parasite genus may have facilitated their diversification across Amazonia, with deep evolutionary history potentially constraining their colonization of Marajó Island.
MOLECULAR PHYLOGENETICS AND EVOLUTION
(2023)
Review
Genetics & Heredity
Jasmita Gill, Anuj Kumar, Amit Sharma
Summary: Nucleosome assembly proteins (NAPs) play a central role in chromatin assembly and disassembly, and their interactions with histones are diverse and complex. Further research is needed to understand the dynamic nature of NAP-histone interactions.
EPIGENETICS & CHROMATIN
(2022)
Article
Biochemistry & Molecular Biology
Hongyu Zhao, Xueqin Shao, Mingxin Guo, Yongqiang Xing, Jingyan Wang, Liaofu Luo, Lu Cai
Summary: Nucleosomes are important for eukaryotic chromatin structure and regulate various biological processes. The histone variant H2A.Z can be dynamically incorporated into nucleosomes to modulate gene expression. Researchers have extended a chemical kinetic model to study the assembly dynamics of H2A.Z-containing nucleosomes. They found that the assembly efficiency of H2A.Z-containing nucleosomes is positively correlated with histone octamer concentration, reaction rate constant, and reaction time. Furthermore, they developed a competitive kinetic model to assess the competitive ability of histones in nucleosome assembly and confirmed that H2A has a higher competitive ability than H2A.Z in vitro. This study demonstrates that the assembly of H2A.Z-containing nucleosomes follows chemical kinetic principles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Hongyu Bao, Massimo Carraro, Valentin Flury, Yanhong Liu, Min Luo, Liu Chen, Anja Groth, Hongda Huang
Summary: This study identifies NASP as a major chaperone protein for H3-H4 histones and uncovers the molecular basis of its role in maintaining histone homeostasis. It reveals two distinct binding modes of NASP and demonstrates the importance of shielding the H3 alpha N region in preserving the soluble pool of H3-H4 histones.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Juste Azelyte, Alejandra Wu-Chuang, Apolline Maitre, Rita Ziegyte, Lourdes Mateos-Hernandez, Dasiel Obregon, Vaidas Palinauskas, Alejandro Cabezas-Cruz
Summary: Avian malaria infection does not significantly change the alpha and beta diversity of the bird gut microbiome, but it does alter the composition and abundance of certain bacterial taxa. The progression of microbiome structural states differs between infected and uninfected birds. Infection by avian malaria parasites is associated with the presence of specific metabolic pathways and the abundance of these pathways changes over the course of infection.
Review
Biochemistry & Molecular Biology
Yaguang Zhang, Qin Zhang, Yang Zhang, Junhong Han
Summary: Histone modification plays a crucial role in regulating replication-coupled nucleosome assembly, DNA damage repair, and gene transcription. Changes or mutations in factors involved in nucleosome assembly are closely associated with the development and pathogenesis of cancer and other human diseases, and are essential for maintaining genomic stability and epigenetic information transmission. This review discusses the impact of various types of histone posttranslational modifications on DNA replication-coupled nucleosome assembly and disease. Furthermore, it summarizes the role of histone modification in the assembly process of DNA replication-coupled nucleosomes, reviews the mechanism of histone modification in cancer development, and briefly introduces the application of histone modification small molecule inhibitors in cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Anna Turkiewicz, Emilia Manko, Damiola R. Oresegun, Debbie Nolder, Anton Spadar, Colin J. Sutherland, Janet Cox-Singh, Robert W. Moon, Yee-Ling Lau, Susana Campino, Taane G. Clark
Summary: The genetic diversity of the zoonotic Plasmodium knowlesi parasite in Southeast Asia has important implications for its evolution, diagnostics, transmission dynamics, and drug resistance. Previous studies have identified three sub-populations of P. knowlesi based on geographical location and macaque host. However, the genetic structure of non-Borneo sub-populations is still unclear. By analyzing a large collection of P. knowlesi whole-genome sequencing data, this study reveals genetic exchange events and differences in different clusters linked to mosquito-related stages and host-related stages.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Vanndita Bahl, Kritika Chaddha, Syed Yusuf Mian, Anthony A. Holder, Ellen Knuepfer, Deepak Gaur
Summary: The novel protein PfMSA180 plays an essential role in parasite egress in Plasmodium falciparum, highlighting its potential as a target for novel malaria intervention strategies.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Chao-Pei Liu, Wenxing Jin, Jie Hu, Mingzhu Wang, Jingjing Chen, Guohong Li, Rui-Ming Xu
Summary: In this study, Liu et al. investigated how sNASP binds H3-H4 in the presence and absence of ASF1, two major histone H3-H4 chaperones found in distinct and common complexes, during chromosomal duplication. They show that, in the presence of ASF1, sNASP principally recognizes a partially unfolded N alpha region of histone H3, and in the absence of ASF1, an additional sNASP binding site becomes available in the core domain of the H3-H4 complex, providing new mechanistic insights into coordinated histone binding and transfer by histone chaperones.
GENES & DEVELOPMENT
(2021)
Review
Biochemistry & Molecular Biology
Shiv I. S. Grewal
Summary: Heterochromatin plays a crucial role in gene regulation, genome integrity, and silencing repetitive DNA elements. Histone modifications, specifically H3K9 methylation, are essential for the establishment and propagation of heterochromatin domains. Recent studies have highlighted the importance of modified histones, particularly H3K9me3, for epigenetic inheritance during cell division. This review discusses key experiments that have demonstrated the significance of modified histones in this process.
Article
Biochemistry & Molecular Biology
Vladyslava Sokolova, Shayan Sarkar, Dongyan Tan
Summary: Histone proteins play important roles in packaging genomic DNA and regulating gene accessibility. Recent cryoelectron microscope studies provide new insights into how histone variants influence the structures and functions of chromatin. This article reviews the current knowledge on histone variants biochemistry and discusses the implications of the new structural information on histone variant biology and their functions in transcription.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Jacob H. Martinsen, Daniel Saar, Catarina B. Fernandes, Benjamin Schuler, Katrine Bugge, Birthe B. Kragelund
Summary: Linker histone H1 plays a role in epigenetic regulation by binding to nucleosomes and altering chromatin structures. Recent research suggests that the number and position of charged side chains on the globular domain of H1 influence chromatin structure and gene repression. By analyzing charge variants of the globular domain, researchers found that modulating the number of charges has little effect on the structure, but affects the stability. This finding helps in understanding the function and structure of H1 histone.
Article
Cell Biology
Ryan L. McCarthy, Kelsey E. Kaeding, Samuel H. Keller, Yu Zhong, Liqin Xu, Antony Hsieh, Yong Hou, Greg Donahue, Justin S. Becker, Oscar Alberto, Bomyi Lim, Kenneth S. Zaret
Summary: McCarthy, Kaeding et al. identified H3K9me3-heterochromatin proteins that repress heterochromatic genes, with ERH playing a key role in global H3K9me3 maintenance in human cells. They also revealed four groups of srHC proteins that repress common genes and repeat elements, expanding our understanding of H3K9me3-based gene repression in vertebrates.
NATURE CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Xuan Ye, Wen Yang, Soon Yi, Yanan Zhao, Gabriele Varani, Eckhard Jankowsky, Fan Yang
Summary: The RRM of RbFox achieves extraordinary sequence specificity by using distinct binding modes for cognate and non-cognate RNAs.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Aline Freville, Margarida Ressurreicao, Christiaan van Ooij
Summary: Malaria parasites alter the host erythrocyte by exporting proteins into it. The presence of a PEXEL motif has been used as a signature for protein export, but this study finds that some proteins remain in the parasitophorous vacuole and are not exported. This challenges the previous understanding of PEXEL and protein processing in malaria parasites.
Review
Pharmacology & Pharmacy
Jasmita Gill, Amit Sharma
Summary: Halofuginone, derived from a Chinese herb, has shown beneficial effects in treating various diseases such as parasitic diseases, cancer, fibrosis, and autoimmune disorders. Its mechanism of action involves inhibiting the prolyl-tRNA synthetase enzyme for its antiparasitic role.
DRUG DISCOVERY TODAY
(2022)
Article
Biochemistry & Molecular Biology
Vivek Kumar Sharma, Swati Gupta, Jyoti Chhibber-Goel, Manickam Yogavel, Amit Sharma
Summary: This study characterizes aspartyl-tRNA synthetase and asparaginyl-tRNA synthetase from Plasmodium falciparum and identifies key residues that determine their specificity towards their respective amino acids.
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Manmohan Sharma, Nachiappan Mutharasappan, Yogavel Manickam, Karl Harlos, Bruno Melillo, Eamon Comer, Heena Tabassum, Suhel Parvez, Stuart L. Schreiber, Amit Sharma
Summary: Bicyclic azetidine compounds have antimalarial activity by targeting the cytoplasmic Plasmodium falciparum protein translation enzyme phenylalanine-tRNA synthetase. A potent inhibitor, BRD7929, was found to bind with high affinity to PfcFRS, exhibiting exquisite specificity compared to the human enzyme. The co-crystal structure of PfcFRS bound with BRD7929 provides insight for the development of novel antimalarial compounds.
Review
Genetics & Heredity
Jasmita Gill, Anuj Kumar, Amit Sharma
Summary: Nucleosome assembly proteins (NAPs) play a central role in chromatin assembly and disassembly, and their interactions with histones are diverse and complex. Further research is needed to understand the dynamic nature of NAP-histone interactions.
EPIGENETICS & CHROMATIN
(2022)
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
Microbiology
Prerna Mandhan, Mansi Sharma, Sushmita Pandey, Neha Chandel, Nidhi Chourasia, Amit Moun, Divyani Sharma, Rubee Sukar, Niyati Singh, Shubhangi Mathur, Aarti Kotnala, Neetu Negi, Ashish Gupta, Anuj Kumar, R. Suresh Kumar, Pramod Kumar, Shalini Singh
Summary: An effective and rapid diagnosis is crucial in controlling the COVID-19 pandemic by isolating infected individuals and providing specialized treatment. Enhanced testing capacity has been proven to effectively curb the transmission of SARS-CoV-2 during the initial phases of outbreaks. However, the cost of molecular diagnosis limits diagnostic capacity in resource-limited countries. This study introduces two pooling strategies, P-5 and P-10, to improve throughput and save resources and time in a high-throughput COVID-19 diagnostic laboratory.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Parasitology
Jasmita Gill, Amit Sharma
Summary: This study analysed global SNPs in aminoacyl-tRNA synthetases (aaRSs), drug targets in malaria parasites. The results showed low mutation frequency in crucial domains and high conservation in drug/substrate binding regions of aaRSs, while another drug target, dihydropteroate synthase (DHPS), showed high mutation occurrences.
PARASITES & VECTORS
(2022)
Article
Microbiology
Soumyananda Chakraborti, Jasmita Gill, Ritu Goswami, Sanjeev Kumar, Anmol Chandele, Amit Sharma
Summary: This study provides structural insights into the implications of RBD mutations in the alpha, delta, and omicron variants of SARS-CoV-2, which were responsible for the surges in India. The analysis identifies key mutations and highlights the importance of electrostatic interactions in stabilizing the RBD-hACE-2-binding.
CURRENT MICROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jasmita Gill, Amit Sharma
Summary: Parasitic diseases pose a significant threat to human health, and the emergence of drug-resistant parasite strains hampers disease control efforts. Aminoacyl-tRNA synthetases (aaRSs) have been identified as potential drug targets due to their vital role in protein synthesis. This study summarizes the progress made in understanding the biochemical characteristics, validation as targets, inhibitor development, and structural interpretation of aaRSs from various parasites responsible for malaria, lymphatic filariasis, giardiasis, toxoplasmosis, leishmaniasis, cryptosporidiosis, and trypanosomiasis. These findings provide a valuable framework for investigating aaRSs from these pathogens and accelerating the development of anti-parasite drugs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Public, Environmental & Occupational Health
Minu Nain, Jasmita Gill, Mradul Mohan, Amit Sharma
Summary: Malaria remains a significant public health issue and relapses caused by dormant liver stages of the Plasmodium parasite hinder control and elimination efforts. The drug of choice for radical cure, Primaquine (PQ), is effective in preventing relapses, but its safety is dependent on the presence of an enzyme called glucose-6-phosphate dehydrogenase (G6PD). G6PD-deficient individuals are at risk of hemolysis when treated with PQ, so it is crucial to study the prevalence of G6PD-deficient genetic variants in endemic populations to assess the risk and explore alternative treatments.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2023)
Article
Biology
Myriam D. Jeninga, Jingyi Tang, Shamista A. Selvarajah, Alexander G. Maier, Michael F. Duffy, Michaela Petter
Summary: The study investigated the epigenetic program underlying the differentiation of male and female gametocytes in Plasmodium falciparum. It identified sex-specific differences in chromatin organization and histone modifications, providing valuable insights into the mechanisms driving sexual differentiation in the parasite.
Article
Infectious Diseases
Jasmita Gill, Amit Sharma
Summary: Plasmodium parasites responsible for malaria interact with human host cells through various surface molecules, including the EPCR receptor. A specific EPCR variant, S219G, has been found to provide protection against severe malaria. Structural analysis reveals that EPCR mutations are mostly located on the receptor surface and are non-conservative. Among the mutations in the EPCR-CIDR alpha 1 interaction region, S88P, L96V/I, and R98L/H/P/C have higher occurrences in diverse populations. These structural insights can guide variant sequencing studies and vaccine development.
INFECTION GENETICS AND EVOLUTION
(2023)
Article
Chemistry, Medicinal
William Nguyen, Madeline G. Dans, Iain Currie, Jon Kyle Awalt, Brodie L. Bailey, Chris Lumb, Anna Ngo, Paola Favuzza, Josephine Palandri, Saishyam Ramesh, Jocelyn Penington, Kate E. Jarman, Partha Mukherjee, Arnish Chakraborty, Alexander G. Maier, Giel G. van Dooren, Tony Papenfuss, Sergio Wittlin, Alisje Churchyard, Jake Baum, Elizabeth A. Winzeler, Delphine Baud, Stephen Brand, Paul F. Jackson, Alan F. Cowman, Brad E. Sleebs
Summary: The discovery of a new class of antimalarial compounds, the 7-N-substituted-3-oxadiazole quinolone, was made through screening the Janssen Jumpstarter library. The optimized compound, WJM228, showed potent antimalarial activity with good metabolic stability in vitro. It was found to target the Q(o) site of cytochrome b and exhibited resistance to drug-resistant parasites.
ACS INFECTIOUS DISEASES
(2023)
Review
Biochemistry & Molecular Biology
Merryn Fraser, Kai Matuschewski, Alexander G. Maier
Summary: Eukaryotic pathogens utilize host cell lipids to establish membrane structures and regulate phospholipid asymmetry to counteract host cell membrane disruption. The interactions between intracellular parasites and host cells are influenced by lipid asymmetry, such as the destruction of infected erythrocytes by phagocytosis due to altered membrane asymmetry. Further research on the dynamics of parasite and host cell phospholipid bilayers is needed to better understand parasitic diseases, host immunity, and immune escape by parasites.
EMERGING TOPICS IN LIFE SCIENCES
(2023)
Article
Microbiology
Jenni A. Hayward, F. Victor M. Makota, Daniela Cihalova, Rachel A. Leonard, Esther Rajendran, Soraya M. J. Zwahlen, Laura G. Shuttleworth, Ursula G. Wiedemann, Christina Spry, Kevin J. Saliba, Alexander G. Maier, Giel G. van Dooren
Summary: Apicomplexans, including the causative agents of malaria and toxoplasmosis, are widespread parasites that pose significant challenges for treatment. The mitochondrial electron transport chain (ETC) has been identified as a potential drug target in these parasites. Using a Seahorse XFe96 flux analyzer, researchers identified six chemically diverse inhibitors of the apicomplexan ETC, at least four of which also targeted the ETC of Plasmodium falciparum. These findings provide new insights into potential treatment options for drug resistant parasites. Evaluation: 10/10.
