A5030887045- Lipid Membrane Structure and Behavior
- Pulmonary Hypertension Research and Treatments
- Ubiquitin and proteasome pathways
- Lipid metabolism and biosynthesis
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Protein Kinase Regulation and GTPase Signaling
- Metabolomics and Mass Spectrometry Studies
- Photosynthetic Processes and Mechanisms
- Advanced Proteomics Techniques and Applications
- Adenosine and Purinergic Signaling
- Trypanosoma species research and implications
- Antibiotic Resistance in Bacteria
- Antimicrobial Resistance in Staphylococcus
- Genomics, phytochemicals, and oxidative stress
- Clostridium difficile and Clostridium perfringens research
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- Chemical Synthesis and Analysis
- Erythrocyte Function and Pathophysiology
- Nanopore and Nanochannel Transport Studies
- Calpain Protease Function and Regulation
- Bioactive Compounds and Antitumor Agents
- Liver Disease Diagnosis and Treatment
- Click Chemistry and Applications
King's College London
2018-2024
Imperial College London
2012-2019
Transnational Press London
2017
Hammersmith Hospital
2017
Elisa (Finland)
2015
Abstract The 23 human zinc finger Asp-His-His-Cys motif-containing (ZDHHC) S -acyltransferases catalyze long-chain -acylation at cysteine residues across an extensive network of hundreds proteins important for normal physiology or dysregulated in disease. Here we present a technology to directly map the protein substrates specific ZDHHC whole-proteome level, intact cells. Structure-guided engineering paired ‘hole’ mutants and ‘bumped’ chemically tagged fatty acid probes enabled probe...
N-Myristoyltransferase (NMT) modulates protein function through the attachment of lipid myristate to N terminus target proteins, and is a promising drug in eukaryotic parasites such as Leishmania donovani. Only small number NMT substrates have been characterized Leishmania, global picture N-myristoylation lacking. Here, we use metabolic tagging with an alkyne-functionalized myristic acid mimetic live followed by downstream click chemistry analysis identify lipidated proteins both...
Clostridium difficile, a leading cause of hospital-acquired infection, possesses dense surface layer (S-layer) that mediates host–pathogen interactions. The key structural components the S-layer result from proteolytic cleavage precursor protein, SlpA, into high- and low-molecular-weight components. Here we report discovery optimization first inhibitors this process in live bacteria their application for probing processing. We also describe design vivo activity-based probes identify protein...
Protein targets of sulforaphane identified, and their affinities quantified, through competition-based chemical proteomics in two live breast cancer cell lines.
RhoB plays a key role in the pathogenesis of hypoxia-induced pulmonary hypertension. Farnesylated promotes growth responses cancer cells and we investigated whether inhibition protein farnesylation will have protective effect.The analysis lung tissues from rodent models hypertensive patients showed increased levels farnesylation. Oral farnesyltransferase inhibitor tipifarnib prevented development hypertension mice. Tipifarnib reduced vascular cell proliferation, endothelium-dependent...
Abstract The 23 human ZDHHC S -acyltransferases catalyze long-chain -acylation at cysteine residues across an extensive network of hundreds proteins important for normal physiology or dysregulated in disease. Here we present a technology platform to directly map the protein substrates specific first time whole proteome level, intact cells. Structure-guided engineering paired ‘hole’ mutants and ‘bumped’ chemically tagged fatty acid probes enabled probe transfer with excellent selectivity over...
RNAi experiments are ubiquitously used in cell biology and achieved by transfection of small interfering RNAs (siRNAs) into cells using a reagent. These results knock-down proteins interest, the phenotypic consequences then analyzed. It is reported here that two common RNA interference (RNAi) reagents, DharmaFECT 1 INTERFERin, mock transfections non-targeting siRNAs, cause alterations lipidome HeLa cells. Some lipids change response to both, presumably chemically different, while other lipid...
Abstract Cells actively maintain complex lipidomes that encompass thousands of lipids, however, many the roles these lipids remain unexplored. Specific interactions between and membrane proteins are a likely reason for evolutionary conservation lipidomes. We report development technique, named lipid-trap mass spectrometry (LTMS), to systematically study protein-lipid directly captured from mammalian cells. LTMS uses immunoprecipitation GFP-tagged expressed in HeLa, followed by lipidomic...
Lipids are key constituents of all cells, which express thousands different lipid species. In most cases, it is not known why cells synthesize such diverse lipidomes, nor what regulates their metabolism. Although that dividing specifically regulate content and the correct complement required for successful division, unclear how lipids connect with cell division machinery. Here, we report membrane protein stomatin involved in cytokinesis step division. a biosynthetic enzyme, depletion causes...
Study objectives: Small GTPase RhoB contributes to pulmonary vascular remodelling in hypertension. Farnesylation of augments cell proliferation while geranylgeranylation is believed be pro-apoptotic. We hypothesized that farnesyltransferase inhibitors may prevent pathology studied the effects inhibitor Tipifarnib on and vasoreactivity chronically hypoxic hypertensive mice cultured human artery endothelial cells (HPAECs). Chemical proteomics was used characterise Tipifarnib-induced changes...