A5052668073- Enzyme Structure and Function
- Photosynthetic Processes and Mechanisms
- Metal-Catalyzed Oxygenation Mechanisms
- Microbial Fuel Cells and Bioremediation
- Microbial metabolism and enzyme function
- Metalloenzymes and iron-sulfur proteins
- Amyotrophic Lateral Sclerosis Research
- Chromium effects and bioremediation
- Biochemical and Molecular Research
- Protein Structure and Dynamics
- Amino Acid Enzymes and Metabolism
- Wastewater Treatment and Nitrogen Removal
- Folate and B Vitamins Research
- Algal biology and biofuel production
- Trace Elements in Health
- Metabolism and Genetic Disorders
- Porphyrin Metabolism and Disorders
- Neurogenetic and Muscular Disorders Research
- Cancer Research and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Microbial Community Ecology and Physiology
- Malaria Research and Control
- Hemoglobin structure and function
- Neurological diseases and metabolism
- ATP Synthase and ATPases Research
University of Liverpool
2016-2025
Health & Life (Taiwan)
2021-2023
Institute of Structural and Molecular Biology
2023
Systems Biology Institute
2023
Institute for Integrative Systems Biology
2020
University of Hong Kong
2020
Institute of Molecular Biology and Biophysics
2017
Daresbury Laboratory
2000-2009
Science and Technology Facilities Council
2008-2009
John Innes Centre
2004-2005
More than 90 point mutations in human CuZn superoxide dismutase lead to the development of familial amyotrophic lateral sclerosis, known also as motor neuron disease. A growing body evidence suggests that a subset located close dimeric interface can major destabilization mutant enzymes. We have determined crystal structures Ala4Val (A4V) and Ile113Thr (I113T) mutants 1.9 1.6 Å, respectively. In A4V structure, small changes at dimer result substantial reorientation two monomers. This effect...
Copper-containing nitrite reductases catalyze the reduction of to nitric oxide (NO), a key step in denitrification that results loss terrestrial nitrogen atmosphere. They are found wide variety denitrifying bacteria and fungi different physiology from range soil aquatic ecosystems. Structural analysis potential intermediates catalytic cycle is an important goal understanding enzyme mechanism. Using "crystal harvesting" substrate-soaking techniques, we have determined atomic resolution...
Mutations in the gene encoding Cu/Zn superoxide dismutase-1 cause amyotrophic lateral sclerosis. Superoxide mutations decrease protein stability and promote aggregation. The mutant monomer is thought to be an intermediate pathway from dimer aggregate. Here we find that monomeric copper-apo, zinc-holo structurally perturbed apo-protein aggregates without reattainment of monomer–dimer equilibrium. Intervention stabilize inhibit aggregation regarded as a potential therapeutic strategy. We...
Superoxide dismutase-1 (SOD1) mutants, including those with unaltered enzymatic activity, are known to cause amyotrophic lateral sclerosis (ALS). Several destabilizing factors contribute pathogenicity a reduced ability complete the normal maturation process which comprises folding, metal cofactor acquisition, intra-subunit disulphide bond formation and dimerization. Immature SOD1 forms toxic oligomers characteristic large insoluble aggregates within motor system cells. Here we report that...
Prion infection is characterized by the conversion of host cellular prion protein (PrP(C)) into disease-related conformers (PrP(Sc)) and can be arrested in vivo passive immunization with anti-PrP monoclonal antibodies. Here, we show that ability an antibody to cure prion-infected cells correlates its binding affinity for PrP(C) rather than PrP(Sc). We have visualized this interaction at molecular level determining crystal structure human PrP bound Fab fragment ICSM 18, which has highest...
Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of progressive neurodegenerative disease amyotrophic lateral sclerosis. Transgenic mice expressing G85R SOD1 variant develop paralytic symptoms concomitant with appearance SOD1-enriched proteinaceous inclusions their neural tissues. The process(es) through which misfolding or aggregation induces motor neuron toxicity is not understood. Here we present structures determined by single crystal...
Significance X-ray crystallography greatly benefits drug discovery work by elucidating information about the binding of compounds to their target. Using this information, changes can be made in a process known as rational design. Cytochrome bc 1 is proven target treatment and prevention malaria, disease that kills over half million people each year many have been developed inhibit cytochrome . Here we show two such crystal structures, which reveal an unexpected site. This opens up new area...
Significance Adult onset neurodegenerative diseases are viewed as protein destabilization, misfolding, and aggregation diseases. TAR DNA binding protein-43 (TDP-43) is strongly associated with many neurological disorders, particularly amyotrophic lateral sclerosis frontotemporal lobar degeneration. All of the disease-associated TDP-43 mutants tested have been shown to increase half-life this correlates inversely age at which sufferer first becomes aware symptoms. Here we show that disease...
Abstract LAT1 (SLC7A5) is a transporter for both the uptake of large neutral amino acids and number pharmaceutical drugs. It expressed in numerous cell types including T-cells, cancer cells brain endothelial cells. However, mechanistic knowledge how it functions its interactions with lipids are unknown or limited due to inability obtaining stable purified protein sufficient quantities. Our data show that depleting cellular cholesterol reduced V max but not K m mediated model substrate into...
Mutations in the gene encoding Cu-Zn superoxide dismutase 1 (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS) cases. A shared effect these mutations is that SOD1, which normally stable dimer, dissociates into toxic monomers seed aggregates. Considerable research effort has been devoted to developing compounds stabilize dimer fALS SOD1 variants, but unfortunately, this not yet resulted treatment. We hypothesized cyclic thiosulfinate cross-linkers, selectively target rare,...