A5009019542- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- Enzyme Structure and Function
- Photosynthetic Processes and Mechanisms
- Prostate Cancer Treatment and Research
- RNA and protein synthesis mechanisms
- Carbohydrate Chemistry and Synthesis
- Protein Structure and Dynamics
- Plant biochemistry and biosynthesis
- Trypanosoma species research and implications
- Bacteriophages and microbial interactions
- Protein Degradation and Inhibitors
- Yersinia bacterium, plague, ectoparasites research
- Microbial Metabolic Engineering and Bioproduction
- Redox biology and oxidative stress
- Peptidase Inhibition and Analysis
- Escherichia coli research studies
- Bacterial Genetics and Biotechnology
- Photoreceptor and optogenetics research
- Trace Elements in Health
- Mosquito-borne diseases and control
- PARP inhibition in cancer therapy
- Cellular Mechanics and Interactions
- Microbial Natural Products and Biosynthesis
- Cancer, Lipids, and Metabolism
University of Glasgow
2010-2024
Cancer Research UK Scotland Institute
2013-2022
Cancer Research UK
2015-2020
Ninewells Hospital
2001-2017
Switch
2013
Institute of Infection and Immunity
2011-2012
University of Dundee
2003-2010
Wellcome Centre for Molecular Parasitology
2006
Mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1/CL100) is an inducible nuclear dual specificity that can dephosphorylate and inactivate both mitogen- stress-activated kinases in vitro vivo. However, the molecular mechanism responsible for substrate selectivity of MKP-1 unknown. In addition, it has been suggested signal transducers activators transcription (STAT1) factor a physiological non-MAP MKP-1. We have used yeast two-hybrid assay to demonstrate able interact selectively...
The C-terminal RING and DTC domains of mammalian Deltex proteins catalyze ADP-ribosylation at the C terminus ubiquitin.
Altered eIF4A1 activity promotes translation of highly structured, eIF4A1-dependent oncogene mRNAs at root oncogenic translational programmes. It remains unclear how these recruit and activate unwinding specifically to facilitate their preferential translation. Here, we show that single-stranded RNA sequence motifs allowing local structural rearrangement in cells. Our data demonstrate contain AG-rich within 5'UTR which structure This mode regulation is used by encoding components...
A class of anti-virulence compounds, the salicylidene acylhydrazides, has been widely reported to block function type three secretion system several Gram-negative pathogens by a previously unknown mechanism. In this work we provide first identification bacterial proteins that are targeted group compounds. We evidence their mode action is likely result from synergistic effect arising perturbation conserved proteins. also examine contribution selected target pathogenicity Yersinia...
Mesenchymal cell motility is driven by polarized actin polymerization [1Olson M.F. Sahai E. The cytoskeleton in cancer motility.Clin. Exp. Metastasis. 2009; 26: 273-287Crossref PubMed Scopus (421) Google Scholar]. Signals at the leading edge recruit machinery to promote membrane protrusion, while matrix adhesion generates tractive force propel forward movement. To work effectively, regulated a complex network of signaling events that affect protein activity and localization. H2O2 has an...
Highlights•Identification of selective UbVs that inhibit or activate RING/U-box E3 ligases•Structural and biochemical analyses reveal mechanisms modulation by UbVs•UbVs CBL UBE4B blocking the E2∼Ub binding site•A UbV dimer stimulates XIAP activity stabilizing E2∼UbSummaryRING U-box ubiquitin ligases regulate diverse eukaryotic processes have been implicated in numerous diseases, but targeting these enzymes remains a major challenge. We report development three variants (UbVs), each...
The C-terminal domain of DELTEX E3s binds ADP-ribose and promotes ubiquitination poly-ADP-ribosylated substrates.
Abstract Ubiquitin (Ub) chain types govern distinct biological processes. K48-linked polyUb chains target substrates for proteasomal degradation, but the mechanism of Ub synthesis remains elusive due to transient nature handover. Here, we present structure a chemically trapped complex E2 UBE2K covalently linked donor and acceptor di-Ub, primed by RING E3. The reveals basis recognition active site residues C-terminal Ub-associated (UBA) domain, impart specificity catalysis. Furthermore,...
Understanding the role of coherent electronic motion is expected to resolve general questions importance in macromolecular energy transfer. We demonstrate a novel nonlinear optical method, angle-resolved wave mixing, that separates out coherently coupled transitions and transfers an instantaneous two-dimensional mapping. Angular resolution signal achieved by using millimeter laser beam waists at sample relay far field; for this we use high energy, ultrabroadband hollow fiber source. reveal...
The ability of any organism to sense and respond challenges presented in the environment is critically important for promoting or restricting colonization specific sites. Recent work has demonstrated that host metabolite D-serine markedly influence outcome infection by repressing type III secretion system enterohaemorrhagic Escherichia coli (EHEC) a concentration-dependent manner. However, exactly how EHEC monitors environmental not understood. In this work, we have identified two highly...
Macrobrachium rosenbergii nodavirus (MrNV) is a pathogen of freshwater prawns that poses threat to food security and causes significant economic losses in the aquaculture industries many developing nations. A detailed understanding MrNV virion structure will inform development strategies control outbreaks. The capsid has also been engineered display heterologous antigens, thus knowledge its atomic resolution benefit efforts develop tools based on this platform. Here, we present an...
// Katerina Mardilovich 1 , Mark Baugh Diane Crighton Dominika Kowalczyk Mads Gabrielsen June Munro Daniel R. Croft Filipe Lourenco James Gabriella Kalna Lynn McGarry Oliver Rath Emma Shanks Mathew J. Garnett 2 Ultan McDermott Joanna Brookfield 3 Charles Tim Hammonds 4 and Michael F. Olson Cancer Research UK Beatson Institute, Garscube Estate, Glasgow, Genome Project, Wellcome Trust Sanger Hinxton, Technology Discovery Laboratories, Jonas Webb Building, Babraham Campus, Cambridge, London...
In the nonmevalonate pathway of isoprenoid biosynthesis, conversion 2 C ‐methyl‐ d ‐erythritol 4‐phosphate into its cyclic diphosphate proceeds via nucleotidyl intermediates and is catalyzed by products ispD , ispE ispF genes. An open reading frame Campylobacter jejuni with similarity to genes Escherichia coli was cloned an expression vector directing formation a 42 kDa protein in recombinant E. strain. The purified shown catalyze transformation 4‐diphosphocytidyl‐2 2‐phosphate...
Prostate cancer affects a large proportion of the male population, and is primarily driven by androgen receptor (AR) activity. First-line treatment typically consists reducing AR signaling hormone depletion, but resistance inevitably develops over time. One way to overcome this issue block function via alternative means, preferably inhibiting protein targets that are more active in tumors than normal tissue. By staining prostate tumor sections, elevated LIM kinase 1 (LIMK1) expression...
The atypical MAP kinases ERK3 and ERK4 are activated by phosphorylation of a serine residue lying within the activation loop signature sequence S-E-G. However, regulation activity is poorly understood. Here we report that inducible nuclear dual-specificity kinase phosphatase (MKP) DUSP2, known regulator ERK p38 MAPKs, unique amongst MKP family in being able to bind both ERK4. This interaction mediated conserved common docking (CD) domain carboxyl-terminal domains motif (KIM) located...
Summary Plasmodium falciparum possesses a single mitochondrion with functional electron transport chain. During respiration, reactive oxygen species are generated that need to be removed protect the organelle from oxidative damage. In absence of catalase and glutathione peroxidase, parasites rely primarily on peroxiredoxin‐linked systems for protection. We have analysed biochemical structural features mitochondrial peroxiredoxin thioredoxin P. . The localization both proteins was confirmed...
In this work, we describe the utility of Light, Oxygen, or Voltage-sensing (LOV) flavoprotein domains from plant phototropins as a reporter for protein expression and function. Specifically, used iLOV, an enhanced more photostable variant LOV. A pET-based plasmid was constructed, encoding C terminal iLOV-octahistidine (His8)-tag HRV 3C protease cleavage recognition site. Ten different proteins, with various sub-cellular locations, were cloned into plasmid, creating iLOV-His8 tag fusions. To...
Fatty acid and retinol-binding proteins (FARs) comprise a family of unusual α-helix rich lipid-binding found exclusively in nematodes. They are secreted into host tissues by parasites plants, animals humans. The structure FAR protein from the free-living nematode Caenorhabditis elegans is available, but this [C. FAR-7 (Ce-FAR-7)] subfamily FARs that does not appear to be important at host/parasite interface. We have therefore examined [Necator americanus FAR-1 (Na-FAR-1)] blood-feeding...
The bifunctional methylerythritol 4-phosphate cytidylyltransferase 2,4-cyclodiphosphate synthase (IspDF) is unusual in that it catalyzes nonconsecutive reactions the 1-deoxy-D-xylulose 5-phosphate (DOXP) pathway of isoprenoid precursor biosynthesis. crystal structure IspDF from bacterial pathogen Campylobacter jejuni reveals an elongated hexamer with D3 symmetry compatible dimeric 2C-methyl-D-erythritol-4-phosphate and trimeric 2C-methyl-D-erythritol-2,4-cyclodiphosphate monofunctional...
The actin cytoskeleton is the chassis that gives a cell its shape and structure, supplies power for numerous dynamic processes including motility, endocytosis, intracellular transport division. To perform these activities, undergoes constant remodelling reorganization. One of major actin-remodelling families are cofilin proteins, made up 1, 2 actin-depolymerizing factor (ADF), which sever aged ADP-associated filaments to reduce filament length provide new potential nucleation sites. Despite...
Mutations in the gene encoding for E3 ubiquitin ligase Parkin have been linked to early-onset Parkinson's disease. Besides many other cellular roles, is involved clearance of damaged mitochondria via mitophagy - a process particular importance dopaminergic neurons. Upon mitochondrial damage, accumulates at outer membrane and activated, leading ubiquitination substrates recruitment effectors. While activation mechanisms autoinhibited extensively studied, it remains unknown how recognises its...
Tryparedoxin (TryX) is a member of the thioredoxin (TrX) fold family involved in regulation oxidative stress parasitic trypanosomatids. Like TrX, TryX carries characteristic Trp-Cys-Xaa-Xaa-Cys motif, which positions redox-active disulfide underneath tryptophan lid. We report structure Crithidia fasciculata tryparedoxin isoform (CfTryX2) two crystal forms and compare them with structures determined previously. Efforts to chemically generate crystals reduced TryX1 were unsuccessful, we...