A5027020217- Antifungal resistance and susceptibility
- Peptidase Inhibition and Analysis
- Fungal Infections and Studies
- Neuropeptides and Animal Physiology
- Antimicrobial Peptides and Activities
- Oral microbiology and periodontitis research
- Protein Kinase Regulation and GTPase Signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Signaling Pathways in Disease
- Enzyme Structure and Function
- Psoriasis: Treatment and Pathogenesis
- Cystic Fibrosis Research Advances
- Neuroinflammation and Neurodegeneration Mechanisms
- Gut microbiota and health
- Flavonoids in Medical Research
- Protein Structure and Dynamics
- Ferrocene Chemistry and Applications
- Berberine and alkaloids research
- Natural product bioactivities and synthesis
- Asthma and respiratory diseases
- Glycosylation and Glycoproteins Research
- Chemical Synthesis and Analysis
- Probiotics and Fermented Foods
- Botulinum Toxin and Related Neurological Disorders
- Ubiquitin and proteasome pathways
King's College London
2018-2023
Imperial College London
2016
Institute for Research in Biomedicine
2007-2011
Candida albicans is a fungal pathobiont, able to cause epithelial cell damage and immune activation. These functions have been attributed its secreted toxin, candidalysin, though the molecular mechanisms are poorly understood. Here, we identify epidermal growth factor receptor (EGFR) as critical component of candidalysin-triggered responses. We find that both C. candidalysin activate human EGFR receptors candidalysin-deficient mutants induce phosphorylation during murine oropharyngeal...
Candida albicans is an opportunistic fungal pathogen responsible for superficial and life-threatening infections in humans. During mucosal infection, C. undergoes a morphological transition from yeast to invasive filamentous hyphae that secrete candidalysin, 31-amino-acid peptide toxin required virulence. Candidalysin damages epithelial cell plasma membranes stimulates the activating protein 1 (AP-1) transcription factor c-Fos (via p38-mitogen-activated kinase [MAPK]), MAPK phosphatase MKP1...
Candidalysin is the first cytolytic peptide toxin identified in any human fungal pathogen. secreted by Candida albicans and critical for driving infection host immune responses several model systems. However,
The fungal pathogen Candida albicans is linked to chronic brain diseases such as Alzheimer's disease (AD), but the molecular basis of anti-Candida immunity remains unknown. We show that C. enters mouse from blood and induces two neuroimmune sensing mechanisms involving secreted aspartic proteinases (Saps) candidalysin. Saps disrupt tight junction proteins blood-brain barrier (BBB) permit invasion. also hydrolyze amyloid precursor protein (APP) into β (Aβ)-like peptides bind Toll-like...
Abstract Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyzes proline‐containing peptides at the carboxy terminus. This has been associated with schizophrenia, bipolar affective disorder, and related neuropsychiatric disorders, therefore may have important clinical implications. Among strategies used to find novel prolyl inhibitors, traditional Chinese medicinal plants provide rich source of unexplored compounds. We 19 F NMR spectroscopy search for new inhibitors in library...
Albumin is abundant in serum but also excreted at mucosal surfaces and enters tissues when inflammation increases vascular permeability. Host-associated opportunistic pathogens encounter albumin during commensalism causing infections. Considering the ubiquitous presence of albumin, we investigated its role pathogenesis infections with model human fungal pathogen, Candida albicans. was introduced various vitro models that mimic different stages systemic or candidiasis, where it reduced...
Prolyl oligopeptidase (POP) is a serine protease highly expressed in the brain that hydrolyses peptide bonds at carboxyl terminal of prolyl residues. There evidence this enzyme participates several functions central nervous system. Scutellaria racemosa Pers demonstrated significant and selective POP inhibition. Fractionation hydroalcoholic extract resulted isolation four main constituents identified for first time from S. Pers, triterpenoid lupeol (1) flavonoids oroxylin A...
Open and closed: The characterization of protein mobility is crucial for the understanding biological functions. We have applied NMR spectroscopy to study conformational dynamics 80 kDa enzyme prolyl oligopeptidase (POP). Our results revealed that POP highly dynamic inhibition catalytic activity shifts this equilibrium towards a less state. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset....
G-protein betagamma (Gbetagamma) subunits interact with a wide range of molecular partners including: G(alpha) subunits, effectors, peptides, and small molecule inhibitors. The mechanisms underlying the ability to accommodate this structurally distinct binding are not well understood. To uncover role protein flexibility alterations in conformation recognition by Gbetagamma, method for site-specific (15)N-labeling Gbeta-Trp residue backbone indole amines insect cells was developed. Transverse...
Prolyl oligopeptidase (POP) and dipeptidyl peptidase IV (DPP IV) are serine proteases that belong to the same family of enzymes. These peptidases relevant because their association with pathophysiology serious illnesses, such as type 2 diabetes IV), those related cognitive disorders (POP). Several NMR-based screening methods being used find validate new hit scaffolds. In particular, (19)F have proven be powerful tools for discovery development inhibitors. Here we present an accurate reliable...
Be selective to simplify: An 15N-label is selectively incorporated into the tryptophan side chains of a large protein and simplified [1H,15N]-TROSY HSQC spectrum obtained without need for deuteration. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note: The publisher responsible content functionality any supporting information supplied Any...