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Articles 1 - 4 of 4
Full-Text Articles in Medicine and Health Sciences
The Sequence Dependent Nanoscale Structure Of Cenp-A Nucleosomes, Tommy Stormberg, Yuri L. Lyubchenko
The Sequence Dependent Nanoscale Structure Of Cenp-A Nucleosomes, Tommy Stormberg, Yuri L. Lyubchenko
Journal Articles: Pharmaceutical Sciences
CENP-A is a histone variant found in high abundance at the centromere in humans. At the centromere, this histone variant replaces the histone H3 found throughout the bulk chromatin. Additionally, the centromere comprises tandem repeats of α-satellite DNA, which CENP-A nucleosomes assemble upon. However, the effect of the DNA sequence on the nucleosome assembly and centromere formation remains poorly understood. Here, we investigated the structure of nucleosomes assembled with the CENP-A variant using Atomic Force Microscopy. We assembled both CENP-A nucleosomes and H3 nucleosomes on a DNA substrate containing an α-satellite motif and characterized their positioning and wrapping efficiency. We …
Peroxide Antimalarial Drugs Target Redox Homeostasis In Plasmodium Falciparum Infected Red Blood Cells, Ghizal Siddiqui, Carlo Giannangelo, Amanda De Paoli, Anna Katharina Schuh, Kim C. Heimsch, Dovile Anderson, Timothy G. Brown, Christopher A. Macraild, Jianbo Wu, Xiaofang Wang, Yuxiang Dong, Jonathan L. Vennerstrom, Katja Becker, Darren J. Creek
Peroxide Antimalarial Drugs Target Redox Homeostasis In Plasmodium Falciparum Infected Red Blood Cells, Ghizal Siddiqui, Carlo Giannangelo, Amanda De Paoli, Anna Katharina Schuh, Kim C. Heimsch, Dovile Anderson, Timothy G. Brown, Christopher A. Macraild, Jianbo Wu, Xiaofang Wang, Yuxiang Dong, Jonathan L. Vennerstrom, Katja Becker, Darren J. Creek
Journal Articles: Pharmaceutical Sciences
Plasmodium falciparum causes the most lethal form of malaria. Peroxide antimalarials based on artemisinin underpin the frontline treatments for malaria, but artemisinin resistance is rapidly spreading. Synthetic peroxide antimalarials, known as ozonides, are in clinical development and offer a potential alternative. Here, we used chemoproteomics to investigate the protein alkylation targets of artemisinin and ozonide probes, including an analogue of the ozonide clinical candidate, artefenomel. We greatly expanded the list of proteins alkylated by peroxide antimalarials and identified significant enrichment of redox-related proteins for both artemisinins and ozonides. Disrupted redox homeostasis was confirmed by dynamic live imaging of the glutathione …
Nanorings To Probe Mechanical Stress Of Single-Stranded Dna Mediated By The Dna Duplex, Karen Zagorski, Tommy Stormberg, Mohtadin Hashemi, Anatoly B. Kolomeisky, Yuri L. Lyubchenko
Nanorings To Probe Mechanical Stress Of Single-Stranded Dna Mediated By The Dna Duplex, Karen Zagorski, Tommy Stormberg, Mohtadin Hashemi, Anatoly B. Kolomeisky, Yuri L. Lyubchenko
Journal Articles: Pharmaceutical Sciences
The interplay between the mechanical properties of double-stranded and single-stranded DNA is a phenomenon that contributes to various genetic processes in which both types of DNA structures coexist. Highly stiff DNA duplexes can stretch single-stranded DNA (ssDNA) segments between the duplexes in a topologically constrained domain. To evaluate such an effect, we designed short DNA nanorings in which a DNA duplex with 160 bp is connected by a 30 nt single-stranded DNA segment. The stretching effect of the duplex in such a DNA construct can lead to the elongation of ssDNA, and this effect can be measured directly using atomic …
Free Cholesterol Accelerates Aβ Self-Assembly On Membranes At Physiological Concentration, Mohtadin Hashemi, Siddhartha Banerjee, Yuri L. Lyubchenko
Free Cholesterol Accelerates Aβ Self-Assembly On Membranes At Physiological Concentration, Mohtadin Hashemi, Siddhartha Banerjee, Yuri L. Lyubchenko
Journal Articles: Pharmaceutical Sciences
The effects of membranes on the early-stage aggregation of amyloid β (Aβ) have come to light as potential mechanisms by which neurotoxic species are formed in Alzheimer's disease. We have shown that direct Aβ-membrane interactions dramatically enhance the Aβ aggregation, allowing for oligomer assembly at physiologically low concentrations of the monomer. Membrane composition is also a crucial factor in this process. Our results showed that apart from phospholipids composition, cholesterol in membranes significantly enhances the aggregation kinetics. It has been reported that free cholesterol is present in plaques. Here we report that free cholesterol, along with its presence inside the …