A5089526494- Nanoplatforms for cancer theranostics
- X-ray Diffraction in Crystallography
- Enzyme Structure and Function
- Nanoparticle-Based Drug Delivery
- Spectroscopy Techniques in Biomedical and Chemical Research
- X-ray Spectroscopy and Fluorescence Analysis
- Advanced Electron Microscopy Techniques and Applications
- Cancer Research and Treatments
- Clostridium difficile and Clostridium perfringens research
- Microbial Metabolic Engineering and Bioproduction
- Advanced X-ray Imaging Techniques
- SARS-CoV-2 and COVID-19 Research
- Climate change and permafrost
- Ion-surface interactions and analysis
- Toxin Mechanisms and Immunotoxins
- Antimicrobial Resistance in Staphylococcus
- Bacteriophages and microbial interactions
- Force Microscopy Techniques and Applications
- Advanced Surface Polishing Techniques
- Machine Learning in Materials Science
- Microbial Metabolism and Applications
- DNA Repair Mechanisms
- Legume Nitrogen Fixing Symbiosis
- Biochemical and biochemical processes
- Click Chemistry and Applications
Diamond Light Source
2019-2024
Newcastle University
2012-2020
Nirmatrelvir (PF-07321332) is a nitrile-bearing small-molecule inhibitor that, in combination with ritonavir, used to treat infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). interrupts the viral life cycle inhibiting SARS-CoV-2 main protease (Mpro), which essential for processing polyproteins into functional nonstructural proteins. We report studies reveal that derivatives of nirmatrelvir and other Mpro inhibitors nonactivated terminal alkyne group positioned...
Summary Engulfment of the forespore by mother cell is a universal feature endosporulation. In Bacillus subtilis , protein SpoIIQ and SpoIIIAH form channel, essential for endosporulation, through which developing spore nurtured. The two proteins also backup system engulfment. Unlike in B. Clostridium difficile has intact LytM zinc‐binding motifs. We show that spoIIQ or spoIIIAH deletion mutants C. result anomalous engulfment, disruption domain via single amino acid substitution (H120S)...
Three-dimensional electron diffraction (3DED) from nanocrystals of biological macromolecules requires the use very small crystals. These are typically less than 300 nm-thick in direction beam due to strong interaction between electrons and matter. In recent years, focused-ion-beam (FIB) milling has been used preparation thin samples for 3DED. instruments a gallium liquid metal ion source. Inductively coupled plasma (ICP) sources principle offer faster rates. Little work done quantify damage...
Abstract The breakdown of fucose and rhamnose released from plant cell walls by the cellulolytic soil bacterium Clostridium phytofermentans produces toxic aldehyde intermediates. To enable growth on these carbon sources, pathway for is encapsulated within a bacterial microcompartment (BMC). These proteinaceous organelles sequester intermediates allow efficient action acylating dehydrogenase enzymes to produce an acyl-CoA that ultimately used in substrate-level phosphorylation ATP. Here we...
With the increasing trend of using microcrystals and intense microbeams at synchrotron X-ray beamlines, radiation damage becomes a more pressing problem. Theoretical calculations show that photoelectrons primarily cause can escape microcrystals. This effect would become pronounced with decreasing crystal size as well higher energies. To prove this effect, data from cryocooled lysozyme crystals dimensions 5 × 3 20 8 µm mounted on cryo-transmission electron microscopy (cryo-TEM) grids were...
The measurement of diffraction data from macromolecular crystal samples held in vacuo holds the promise a very low X-ray background and zero absorption incident scattered beams, leading to better potential for accessing long wavelengths (>3 Å) native sulfur phasing. Maintaining hydration protein crystals under vacuum is achieved by use liquid jets, as with serial collection at free-electron lasers, or side-stepped cryocooling samples, implemented new synchrotron beamlines. Graphene has been...
Developing methods to determine high-resolution structures from micrometre- or even submicrometre-sized protein crystals has become increasingly important in recent years. This applies both large complexes and membrane proteins, where production the subsequent growth of homogeneous is often challenging, samples which yield only micro- nanocrystals such as amyloid viral polyhedrin proteins. The versatile macromolecular crystallography microfocus (VMXm) beamline at Diamond Light Source...
The mounting of microcrystals (<10 µm) for single crystal cryo-crystallography presents a non-trivial challenge. Improvements in data quality have been seen with the development beamline optics, beam stability and variable size focusing from submicron to microns, such as at VMXm Diamond Light Source1. Further improvements will be gained through sample environment preparation. Microcrystals inherently generate weaker diffraction, therefore improving signal-to-noise is key collecting X-ray...
Abstract Infectious protein crystals are an essential part of the viral lifecycle for double-stranded DNA Baculoviridae and RNA cypoviruses. These crystals, termed occlusion bodies or polyhedra, dense assemblies that form a crystalline array, encasing newly formed virions. Here, using X-ray crystallography we determine structure polyhedrin from Nudiviridae . This virus family is sister-group to baculoviruses, whose members were thought lack bodies. The 70-year-old sample contains...
Many biologists are now routinely seeking to determine the three-dimensional structures of their proteins choice, illustrating importance this knowledge, but also simplification and streamlining structure-determination processes. Despite fact that most software packages offer simple pipelines, for non-expert navigating outputs understanding key aspects can be daunting. Here, structure determination type IV pili (TFP) protein PilA1 from Clostridioides difficile is used illustrate different...
The mounting of microcrystals (<10 µm) for single crystal cryo-crystallography presents a non-trivial challenge. Improvements in data quality have been seen with the development beamline optics, beam stability and variable size focusing from submicron to microns, such as at VMXm Diamond Light Source1. Further improvements will be gained through sample environment preparation. Microcrystals inherently generate weaker diffraction, therefore improving signal-to-noise is key collecting X-ray...
VMXm joins the suite of operational macromolecular crystallography beamlines at Diamond Light Source. It has been designed to optimize rotation data collections from protein crystals less than 10 µm and down below 1 in size. The beamline a fully focused beam 0.3 × 2.3 (vertical horizontal) with tuneable energy range (6–28 keV) high flux (1.6 12 photons s −1 12.5 keV). are housed within vacuum chamber minimize background scatter air. Crystals plunge-cooled on cryo-electron microscopy grids,...