A5050259118- Ion Channels and Receptors
- Meat and Animal Product Quality
- Bacterial Genetics and Biotechnology
- Cystic Fibrosis Research Advances
- Calcium signaling and nucleotide metabolism
- Protein Structure and Dynamics
- Ion channel regulation and function
- Anesthesia and Sedative Agents
- RNA and protein synthesis mechanisms
- Anesthesia and Neurotoxicity Research
- Piperaceae Chemical and Biological Studies
- Cardiac, Anesthesia and Surgical Outcomes
- Metabolism and Genetic Disorders
- Advanced Chemical Sensor Technologies
- Gallbladder and Bile Duct Disorders
- Neonatal Respiratory Health Research
- Respiratory Support and Mechanisms
- Airway Management and Intubation Techniques
- Microbial Inactivation Methods
- Medical and Biological Sciences
- Identification and Quantification in Food
- Mitochondrial Function and Pathology
- Abdominal Surgery and Complications
- Pediatric Hepatobiliary Diseases and Treatments
- Biliary and Gastrointestinal Fistulas
Semmelweis University
2014-2024
Montavid Thermodynamic Research Group
2023
Hungarian Academy of Sciences
2014-2020
Medical University Plovdiv
2020
International Business School
2018
Université de Toulouse
2012-2017
Institut de Pharmacologie et de Biologie Structurale
2012-2017
Centre National de la Recherche Scientifique
2012-2017
Université Toulouse III - Paul Sabatier
2012-2017
Bulgarian Academy of Sciences
1998-2010
Itaconate is a nonamino organic acid exhibiting antimicrobial effects. It has been recently identified in cells of macrophage lineage as product an enzyme encoded by immunoresponsive gene 1 (Irg1), acting on the citric cycle intermediate cis-aconitate. In mitochondria, itaconate can be converted succinate-coenzyme A (CoA) ligase to itaconyl-CoA at expense ATP (or GTP), and also weak competitive inhibitor complex II. Here, we investigated specific bioenergetic effects increased production...
Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable cation channel implicated in postischemic neuronal cell death, leukocyte activation, and insulin secretion, is activated by intracellular ADP ribose (ADPR). In addition, the pyridine dinucleotides nicotinamide-adenine-dinucleotide (NAD), nicotinic acid–adenine-dinucleotide (NAAD), NAAD-2′-phosphate (NAADP) have been shown to activate TRPM2, or enhance its activation ADPR, when dialyzed into cells. The precise subset of...
Transient Receptor Potential Melastatin 2 (TRPM2) is a Ca2+-permeable cation channel essential for immunocyte activation, insulin secretion, and postischemic cell death. TRPM2 activated by ADP ribose (ADPR) binding to its C-terminal cytosolic NUDT9-homology (NUDT9H) domain, homologous the soluble mitochondrial ADPR pyrophosphatase (ADPRase) NUDT9. Reported hydrolysis classified as channel-enzyme, but insolubility of isolated NUDT9H hampered further investigations. Here we developed model...
The role of membrane proteins in cellular mechanism strongly depends on their dynamics, and solid-state magic-angle spinning (MAS) nuclear magnetic resonance (NMR) is a unique method to exhaustively characterize motions lipid environment. Herein, we make use advances 1H-detected MAS NMR describe the dynamics domain Outer protein A Klebsiella pneumoniae (KpOmpA). By measuring 1H-15N dipolar-coupling as well 15N R1 R1ρ relaxation rates at fast (60 kHz) high field (1 GHz), were able residues...
Significance Ion channels are protein pores that pass ions across biological membranes. CFTR is an anion channel required for proper salt–water transport epithelia, including the lung and gut. overactivation due to bacterial toxins causes severe diarrhea (e.g., in cholera), impaired activation mutations underlies cystic fibrosis, a lethal disease. activated by kinase (PKA) which phosphorylates channel. Here we show not caused phosphorylation, as believed, but simple PKA binding promotes...
Protein kinase A (PKA) is a key regulator of cellular functions by selectively phosphorylating numerous substrates, including ion channels, enzymes, and transcription factors. It has long served as model system for understanding the eukaryotic kinases. Using cryoelectron microscopy, we present complex structures PKA catalytic subunit (PKA-C) bound to full-length protein substrate, cystic fibrosis transmembrane conductance (CFTR)—an channel vital human health. CFTR gating requires...
Significance Ion channels are protein pores that allow passive transmembrane ion flow. These opened and closed (gated) by various cellular signals. Typically, the mechanism of gating conformational changes is an equilibrium process, but for some channels, irreversible cycle, example, linked to enzymatic activity. For mechanisms, channel activity readily modulated energetic stabilization or open states, whereas cyclic gating, alteration transition-state stabilities most effectively modulates...
Summary Protein kinase A (PKA) is a key regulator of cellular functions by selectively phosphorylating numerous substrates, including ion channels, enzymes, and transcription factors. It has long served as model system for understanding the eukaryotic kinases. Using cryo-electron microscopy, we present complex structures PKA catalytic subunit (PKA-C) bound to full-length protein substrate, cystic fibrosis transmembrane conductance (CFTR) – an channel vital human health. CFTR gating requires...
Succinate-CoA ligase (SUCL) is a heterodimer enzyme composed of Suclg1 α-subunit and substrate-specific Sucla2 or Suclg2 β-subunit yielding ATP GTP, respectively. In humans, the deficiency this leads to encephalomyopathy with without methylmalonyl aciduria, in addition resulting mitochondrial DNA depletion. We generated mice lacking either one allele. heterozygote exhibited tissue- age-dependent decreases expression associated ATP-forming activity, but rebound increases cardiac GTP-forming...
Transient Receptor Potential Melastatin 2 (TRPM2) is a cation channel important for the immune response, insulin secretion, and body temperature regulation. It activated by cytosolic ADP ribose (ADPR) contains nudix-type motif 9 (NUDT9)-homology (NUDT9-H) domain homologous to ADPR phosphohydrolases (ADPRases). Human TRPM2 (hsTRPM2) catalytically inactive due mutations in conserved Nudix box sequence. Here, we show that motifs are canonical all invertebrates but vestigial vertebrates....
Transient receptor potential melastatin 2 (TRPM2) is a homotetrameric Ca2+-permeable cation channel important for the immune response, body temperature regulation, and insulin secretion, activated by cytosolic Ca2+ ADP ribose (ADPR). ADPR binds to two distinct locations, formed large N- C-terminal domains, respectively, of protein. In invertebrate TRPM2 channels, site not required activity but acts as an active phosphohydrolase that cleaves activating ligand. vertebrate catalytically...
In the present study it is shown that poloxamer 188, added before or immediately after an electrical pulse used for electroporation, decreases number of dead cells and at same time does not reduce reversible electropores through which small molecules (cisplatin, bleomycin, propidium iodide) can pass/diffuse. It was suggested hydrophobic sections 188 are incorporated into edges pores their hydrophilic parts act as brushy pore structures. The formation may expansion delay irreversible...
Abstract CFTR, the anion channel mutated in cystic fibrosis (CF) patients, is activated by catalytic subunit of protein kinase A (PKA-C). PKA-C activates CFTR both reversibly, through binding, and irreversibly, phosphorylation multiple serines CFTR’s regulatory (R) domain. Here we identify key molecular determinants CFTR/PKA-C interaction essential for these processes. By comparing current activation presence ATP or an analog unsuitable phosphotransfer, as well pseudosubstrate peptides...
The series of complexes: cis-[Pd(PMSA) 2 X ], cis-[Pt(PMSA) trans-[Pt(PMSA) I ] and [Pt(PMSA) 4 ]Cl (PMSA = N-3-pyridinylmethanesulfonamide; Cl, Br, I), previously synthesized characterized by us, as well the free ligand PMSA, were tested for their cytotoxic activity without electroporation - against murine leukemia F4N human SKW-3 MDA-MB-231 tumour cell lines with latter two lines. majority complexes exhibited effects (IC 50 < 100 μmol/l) under conditions electroporation. Both cis- had...
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), the anion channel mutated in cystic fibrosis (CF) patients, is activated by catalytic subunit of protein kinase A (PKA-C). PKA-C activates CFTR both noncatalytically, through binding, and catalytically, phosphorylation multiple serines CFTR’s regulatory (R) domain. Here, we identify key molecular determinants CFTR/PKA-C interaction essential for these processes. By comparing current activation presence ATP or an analog unsuitable...
CFTR, the anion channel mutated in cystic fibrosis patients, is a model ABC protein whose ATP-driven conformational cycle observable at single-molecule level patch-clamp recordings. Bursts of CFTR pore openings are coupled to tight dimerization its two nucleotide-binding domains (NBDs) and wild-type (WT) channels mostly terminated by ATP hydrolysis. The slow rate non-hydrolytic closure - which determines how tightly bursts hydrolysis unknown, as burst durations catalytic site mutants span...