A5062453474- Glutathione Transferases and Polymorphisms
- Asthma and respiratory diseases
- Pharmacogenetics and Drug Metabolism
- Genomics, phytochemicals, and oxidative stress
- Polyamine Metabolism and Applications
- DNA Repair Mechanisms
- Mast cells and histamine
- Eosinophilic Esophagitis
- Bacterial Genetics and Biotechnology
- Eosinophilic Disorders and Syndromes
- Research on Leishmaniasis Studies
- Drug Transport and Resistance Mechanisms
- Amino Acid Enzymes and Metabolism
- Inflammatory mediators and NSAID effects
- Monoclonal and Polyclonal Antibodies Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Metabolomics and Mass Spectrometry Studies
- Epigenetics and DNA Methylation
- Bacteriophages and microbial interactions
- Circadian rhythm and melatonin
- Drug-Induced Hepatotoxicity and Protection
- Porphyrin Metabolism and Disorders
- Eicosanoids and Hypertension Pharmacology
- Tryptophan and brain disorders
Karolinska Institutet
2015-2022
Madurai Kamaraj University
2017
Division of Chemistry
2016
Karolinska University Hospital
2015
Science for Life Laboratory
2015
Fraunhofer Institute for Molecular Biology and Applied Ecology
2015
Microsomal glutathione S-transferase 2 (MGST2) produces leukotriene C4, key for intracrine signaling of endoplasmic reticulum (ER) stress, oxidative DNA damage and cell death. MGST2 trimer restricts catalysis to only one out three active sites at a time, but the molecular basis is unknown. Here, we present crystal structures human combined with biochemical computational evidence concerted mechanism, involving local unfolding coupled global conformational changes that regulate catalysis....
SUCNR1 is a sensor of extracellular succinate, Krebs cycle intermediate generated in excess during oxidative stress and has been linked to metabolic regulation inflammation. While mast cells express SUCNR1, its role cell reactivity allergic conditions such as asthma remains be elucidated.Cord blood-derived human line LAD-2 challenged by ligands were analyzed for the activation mediator release. Effects on cell-dependent bronchoconstriction assessed guinea pig trachea isolated small bronchi...
Cysteinyl leukotrienes (cys-LTs) are lipid mediators of inflammation. The enzyme catalyzing synthesis cys-LTs, leukotriene C<sub>4</sub> synthase (LTC4S), is considered an important drug target. Here we report the and characterization three tandem benzophenone amino pyridines as inhibitors LTC4S in vitro vivo. were characterized using recombinant human LTC4S, MonoMac 6 cells, a panel peripheral immune cells. In vivo, compounds tested Zymosan A-induced peritonitis mouse model. molecules,...
Leukotriene C4 synthase (LTC4S) catalyzes the formation of proinflammatory lipid mediator leukotriene (LTC4). LTC4 is parent molecule cysteinyl leukotrienes, which are recognized for their pathogenic role in asthma and allergic diseases. Cellular LTC4S activity suppressed by PKC-mediated phosphorylation, recently a downstream p70S6k was shown to play an important this process. Here, we identified Ser(36) as major phosphorylation site, along with low frequency site at Thr(40), using vitro...
Drug-induced toxicity has, in many cases, been linked to oxidative metabolism resulting the formation of reactive metabolites and subsequent covalent binding biomolecules. Two structurally related antipsychotic drugs, clozapine (CLZ) olanzapine (OLZ), are known form similar nitrenium ion metabolites. CLZ-derived have agranulocytosis hepatotoxicity. We studied CLZ OLZ as well two CLZ, desmethyl-CLZ (DCLZ), CLZ-N-oxide (CLZ-NO), using vitro rat liver microsomal (RLM) incubations with...
Abstract Both soluble and membrane-bound enzymes can catalyze the conversion of lipophilic substrates. The precise substrate access path, with regard to phase, has however, until now relied on conjecture from enzyme structural data only (certainly giving credible valuable hypotheses). Alternative methods have been missing. To obtain first experimental evidence directly determining paths (of substrates) phase constrained we here describe application a BODIPY-derived (PS1). Using this tool,...
Porins form trimers in the outer membrane and help transport nutrients waste products across bacterial cell membrane. Porin loops are suitable candidates as display systems due to their high immunogenicity presentation at surface. In this study, Salmonella typhi porins (OmpC OmpF) engineered with Kennedy peptide from gp41 of HIV were characterised. The chimeric OmpC carrying loop7 did not trimerise, whereas OmpF epitope loop5 formed also was recognised by antibodies patient serum. results...
Abstract Acetaminophen (APAP)‐related toxicity is caused by the formation of N ‐acetyl p ‐benzoquinone imine (NAPQI), a reactive metabolite able to covalently bind protein thiols. A targeted liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method, using multiple reaction monitoring (MRM), was developed measure APAP binding on selected target proteins, including glutathione S ‐transferases (GSTs). In vitro incubations with CYP3A4 were performed form in presence different four...