A5029091774- DNA and Nucleic Acid Chemistry
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- Lepidoptera: Biology and Taxonomy
- Genomics and Chromatin Dynamics
- HIV/AIDS drug development and treatment
- Force Microscopy Techniques and Applications
- Insect Pheromone Research and Control
- Bacterial Genetics and Biotechnology
- DNA Repair Mechanisms
- Plant and animal studies
- Entomological Studies and Ecology
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Protein Structure and Dynamics
- Metal complexes synthesis and properties
- Birth, Development, and Health
- Monoclonal and Polyclonal Antibodies Research
- Species Distribution and Climate Change
- Pregnancy and preeclampsia studies
- Nanopore and Nanochannel Transport Studies
Northeastern University
2016-2025
Caterpillar (United States)
2022
Dermatology Society of South Africa
2022
Imperial College London
2022
University of Nevada, Reno
2021
Diamond Light Source
2020
University of South Wales
2018-2019
University of Pretoria
1990-2019
Boston University
2010-2019
AECOM (China)
2010-2017
Abstract APOBEC3G (A3G), a host protein that inhibits HIV-1 reverse transcription and replication in the absence of Vif, displays cytidine deaminase single-stranded (ss) nucleic acid binding activities. nucleocapsid (NC) also binds acids has unique property, chaperone activity, which is crucial for efficient transcription. Here we report interplay between A3G, NC transcriptase (RT) effect highly purified A3G on individual reactions occur during We find did not affect kinetics NC-mediated...
There is a wide range of applications for non-covalent DNA binding ligands, and optimization such interactions requires detailed understanding the mechanisms. One important class these ligands that intercalators, which bind by inserting aromatic moieties between adjacent base pairs. Characterizing dynamic equilibrium aspects DNA-intercalator complex assembly may allow specific functions. Single-molecule force spectroscopy studies have recently revealed new details about molecular mechanisms...
HIV-1 cores, which contain the viral genome and replication machinery, must disassemble (uncoat) during replication. However, host factors that trigger uncoating remain unidentified. Recent studies show infectious cores enter nucleus uncoat near site of integration. Here, we efficient nuclear requires synthesis a double-stranded DNA (dsDNA) >3.5 kb efficiency correlates with size. Core disruption by capsid inhibitors releases DNA, some integrates. most is degraded, indicating intact core...
The nucleocapsid protein (NC) of HIV type 1 is a nucleic acid chaperone that facilitates the rearrangement acids into conformations containing maximum number complementary base pairs. We use an optical tweezers instrument to stretch single DNA molecules from helix coil state at room temperature in presence NC and mutant form (SSHS NC) lacks two zinc finger structures present NC. Although both SSHS facilitate annealing strands through electrostatic attraction, only destabilizes helical...
The history of drug discovery spans approximately 200,000 years. For much this time, the identification therapeutic agents was empirical, with shift to a more hypothesis-driven approach occurring in late 19th century. Since then, objective has changed from identifying an active and its mechanism action determining potential only after drug-like compounds that interact target site. Although emphasis on identification, or "targephilia," yielded novel drugs, overall it appears have slowed...
Phenanthriplatin, a monofunctional anticancer agent derived from cisplatin, shows significantly more rapid DNA covalent-binding activity compared to its parent complex. To understand the underlying molecular mechanism, we used single-molecule studies with optical tweezers probe kinetics of DNA-phenanthriplatin binding as well several control complexes. The time-dependent extensions single λ-DNA molecules were monitored at constant applied forces and compound concentrations, followed by...
The SARS-CoV-2 nucleocapsid (N) protein performs several functions including binding, compacting, and packaging the ∼30 kb viral genome into particle. N consists of two ordered domains, with terminal domain (NTD) primarily associated RNA binding C (CTD) dimerization/oligomerization, three intrinsically disordered regions, an N-arm, a C-tail, linker that connects NTD CTD. We utilize optical tweezers system to isolate long single-stranded nucleic acid substrate measure directly function at...
Expansion of ecotourism-based industries, changes in land-use practices, and escalating competition for resources have increased contact between free-ranging wildlife humans. Although human presence areas may provide an important economic benefit through ecotourism, exposure to pathogens represent a health risk wildlife. This report is the first document introduction primary pathogen into We describe outbreaks Mycobacterium tuberculosis, pathogen, banded mongooses (Mungos mungo) Botswana...
The nucleocapsid protein (NC) of HIV type 1 (HIV-1) is a nucleic acid chaperone that facilitates the rearrangement secondary structure during reverse transcription. HIV-1 NC contains two CCHC-type zinc binding domains. Here, we use optical tweezers to stretch single λ-DNA molecules through helix-to-coil transition in presence wild-type and several mutant forms with altered zinc-finger Although all lowered cooperativity DNA helix–coil transition, subtle changes structures reduced NC's effect...
When a single DNA molecule is stretched beyond its normal contour length, force-induced melting transition observed. Ethidium binding increases the decreases elongation upon melting, and force in manner that consistent with ethidium-induced changes duplex stability known from thermal studies. The stretching curves map out phase diagram critical point force-extension-ethidium concentration space. Intercalation occurs between alternate base pairs at low forces every pair high forces.
Here we explore DNA binding by a family of ruthenium(II) polypyridyl complexes using an atomic force microscope (AFM) and optical tweezers. We demonstrate AFM that Ru(bpy)2dppz2+ intercalates into (Kb = 1.5 × 105 M-1), as does its close relative Ru(bpy)2dppx2+ M-1). However, intercalation Ru(phen)32+ other Ru(II) with Kb values lower than is difficult to determine because competing aggregation surface-binding phenomena. At the high concentrations required evaluate intercalation, most strands...
Human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein (NC) is a nucleic acid chaperone that facilitates the remodeling of acids during various steps viral life cycle. Two main features NC's activity are its abilities to aggregate and destabilize acids. These functions associated with highly basic character zinc finger domains, respectively. While HIV-1 NC has been extensively studied, less known about activities other retroviral NCs. In this work, complementary experimental...
AMP-activated kinase (AMPK) is central to sensing energy status in eukaryotic cells via binding of AMP and ATP CBS (cystathionine beta-synthase) domains the regulatory gamma subunit. The structure a CBS-domain pair from human AMPK gamma1 complex with physiological activator pharmacological ZMP (AICAR) presented.