- Advanced NMR Techniques and Applications
- Amino Acid Enzymes and Metabolism
- Bacterial Genetics and Biotechnology
- Protein Structure and Dynamics
- Electron Spin Resonance Studies
- RNA and protein synthesis mechanisms
- Drug Transport and Resistance Mechanisms
- Lipid Membrane Structure and Behavior
- Advanced MRI Techniques and Applications
- Adenosine and Purinergic Signaling
- Enzyme Structure and Function
- Antibiotic Resistance in Bacteria
- DNA and Nucleic Acid Chemistry
- Muon and positron interactions and applications
- Solid-state spectroscopy and crystallography
- Trace Elements in Health
- Receptor Mechanisms and Signaling
- Chemical Reactions and Isotopes
- Carbohydrate Chemistry and Synthesis
- Machine Learning in Bioinformatics
- Escherichia coli research studies
- Bacteriophages and microbial interactions
- Mass Spectrometry Techniques and Applications
- Chemical Synthesis and Analysis
- Polyamine Metabolism and Applications
University of Leeds
2015-2024
Institute of Structural and Molecular Biology
2014-2024
Hamedan University of Medical Sciences
2015
University of Surrey
2012
University of Liverpool
2008
Diamond Light Source
2008
Imperial College London
2008
Japan Science and Technology Agency
2008
Kyoto University
2008
University of Manchester
2004
The nucleobase-cation-symport-1 (NCS1) transporters are essential components of salvage pathways for nucleobases and related metabolites. Here, we report the 2.85-angstrom resolution structure NCS1 benzyl-hydantoin transporter, Mhp1, from Microbacterium liquefaciens. Mhp1 contains 12 transmembrane helices, 10 which arranged in two inverted repeats five helices. structures outward-facing open substrate-bound occluded conformations were solved, showing how cavity closes upon binding substrate....
Chlorhexidine is widely used as an antiseptic or disinfectant in both hospital and community settings. A number of bacterial species display resistance to this membrane-active biocide. We examined the transcriptomic response a representative nosocomial human pathogen, Acinetobacter baumannii, chlorhexidine identify primary elements. The most highly up-regulated genes encoded components major multidrug efflux system, AdeAB. next overexpressed gene under stress was annotated encoding...
The hydantoin transporter Mhp1 is a sodium-coupled secondary active transport protein of the nucleobase-cation-symport family and member widespread 5-helix inverted repeat superfamily transporters. structure was previously solved in three different conformations providing insight into molecular basis alternating access mechanism. Here, we elucidate detailed events substrate binding, through combination crystallography, dynamics, site-directed mutagenesis, biochemical/biophysical assays,...
Nuclear magnetic resonance (NMR) spectroscopy is a powerful non-invasive analytical technique with wide applications that can observe multiple nuclear species at site-resolved level. Despite this, NMR has inherent low sensitivity compared to other techniques. A principal approach improve the and resolution of experiment increase strength external static field (B0), for which upper practicable limit gradually increased over five decades. The relatively recent use high-temperature...
Tribulus terrestris is a member of the family Zygophyllaceae commonly known as “puncture vine”. The plant has been used traditionally an analgesic and to relieve rheumatic pain, eye problems, sexual dysfunction edema. aim this work was test use T. fruit extract reducing agent in synthesizing gold nanoparticles (AuNPs), their biological activities, assess suitability therapeutic by testing them for potential adverse effects on human cells. Indeed, we have performed most comprehensive AuNPs...
A series of 46 natural nucleosides and analogues (mainly adenosine-based) were tested as inhibitors [U-14C]uridine uptake by the concentrative, H+-linked nucleoside transport proteins NupC NupG from Escherichia coli. The two evolutionarily unrelated transporters showed similar but distinct patterns inhibition, revealing differing selectivities for different their analogues. Binding to required presence hydroxyl groups at each C-3′ C-5′ positions ribose, while binding only substituent....
We report a comprehensive analysis of the numbers, lengths and amino acid compositions transmembrane helices in 235 high-resolution structures integral membrane proteins. The properties 1551 were compared with those obtained by same sequences using topology prediction tools. Explanations for 81 (5.2%) missing or additional results identified. Main reasons mis-identification N-terminal signal peptides, breaks α-helix conformation charged residues middle unusual composition. main reason was...
This chapter gives an overview and describes the current status future potential for solid‐state nuclear magnetic resonance (NMR) spectroscopy in drug design discovery. Using illustrated examples, it deals first with unique roles that technique can provide pharmaceutical development process, including characterization analysis of compound polymorphism, chiral purity quantitation, use “NMR crystallography” solving structures small organic molecules, polymers, biomacromolecules. It then...
This work reports the evolutionary relationships, amplified expression, functional characterization and purification of putative allantoin transport protein, PucI, from Bacillus subtilis. Sequence alignments phylogenetic analysis confirmed close relationships between PucI membrane proteins nucleobase-cation-symport-1 family secondary active transporters. These include sodium-coupled hydantoin Mhp1, Microbacterium liquefaciens, related bacteria, fungi plants. Membrane topology predictions for...
NupG from Escherichia coli is the archetype of a family nucleoside transporters found in several eubacterial groups and has distant homologues eukaryotes, including man. To facilitate investigation its molecular mechanism, we developed methods for expressing an oligohistidine-tagged form both at high levels (>20% inner membrane protein) E. Xenopus laevis oocytes. In recombinant transported purine (adenosine) pyrimidine (uridine) nucleosides with apparent K(m) values approximately 20-30...
VanA-type resistance to glycopeptide antibiotics in clinical enterococci is regulated by the VanS
Nuclear magnetic resonance (NMR) spectroscopy is a principal well-established technique for analysis of chemical, biological, food and environmental samples.This article provides an overview the properties applications NMR-active nuclei (39 33 different elements) used in NMR measurements (solution-and solid-state NMR, spectroscopy, imaging) with biological biomedical systems samples.The samples include biofluids, cells, tissues, organs or whole body from organisms (humans, animals, bacteria,...
An experimental approach is described in which high resolution 13C solid-state NMR (SSNMR) spectroscopy has been used to detect interactions between specific residues of membrane-embedded transport proteins and weakly binding noncovalent ligands. This procedure provided insight into the site for substrate d-glucose Escherichia coli sugar protein GalP. Cross-polarization magic-angle spinning (CP-MAS) SSNMR spectra GalP its natural membrane at 4 °C indicated that α- β-anomers d-[1-13C]glucose...