A5076021638- Hemoglobin structure and function
- Erythrocyte Function and Pathophysiology
- Protein Structure and Dynamics
- Redox biology and oxidative stress
- Enzyme function and inhibition
- Neonatal Health and Biochemistry
- Heme Oxygenase-1 and Carbon Monoxide
- Porphyrin Metabolism and Disorders
- Photosynthetic Processes and Mechanisms
- Microbial metabolism and enzyme function
- Glutathione Transferases and Polymorphisms
- Parasites and Host Interactions
- Research on Leishmaniasis Studies
- Hemoglobinopathies and Related Disorders
- Biochemical Acid Research Studies
- Metal-Catalyzed Oxygenation Mechanisms
- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Nitric Oxide and Endothelin Effects
- Mass Spectrometry Techniques and Applications
- Blood properties and coagulation
- Trace Elements in Health
- Toxin Mechanisms and Immunotoxins
- Enzyme-mediated dye degradation
- Drug Transport and Resistance Mechanisms
Sapienza University of Rome
2015-2025
Istituto Pasteur
2004-2017
Institute of Molecular Biology and Pathology
2003-2012
National Research Council
2012
Parker Hannifin (United States)
2009
Miele (Germany)
2009
Bernhard Nocht Institute for Tropical Medicine
2004
University of Cagliari
1985-2003
University of Rome Tor Vergata
1985-2003
Institut Pasteur de Lille
2003
Schistosomiasis is a parasitic disease affecting over 200 million people currently treated with one drug, praziquantel. A possible drug target the seleno-protein thioredoxin-glutathione reductase (TGR), key enzyme in pathway of parasite for detoxification reactive oxygen species. The unique fusion glutaredoxin domain thioredoxin domain, which contains selenocysteine (Sec) as penultimate amino acid. Auranofin (AF), gold-containing compound already clinical use an anti-arthritic has been shown...
The reaction of cyanide metmyoglobin with dithionite conforms to a two-step sequential mechanism formation an unstable intermediate, identified as bound ferrous myoglobin. This was investigated by stopped-flow time resolved spectroscopy using different myoglobins, i.e. those from horse heart, Aplysia limacina buccal muscle, and three recombinant derivatives sperm whale skeletal muscle myoglobin (Mb) (the wild type two mutants). myoglobins (wild type) have in the distal position (E7) histidyl...
Schistosomiasis is the second most widespread human parasitic disease. It principally treated with one drug, praziquantel, that administered to 100 million people each year; less sensitive strains of schistosomes are emerging. One appealing drug targets against schistosomiasis thioredoxin glutathione reductase (TGR). This natural chimeric enzyme a peculiar fusion glutaredoxin domain selenocysteine (U)-containing domain. Selenocysteine located on flexible C-terminal arm usually disordered in...
Cd 1 nitrite reductase catalyzes the conversion of to NO in denitrifying bacteria. Reduction substrate occurs at d -heme site, which faces on distal side some residues thought be essential for binding and catalysis. We report results obtained by mutating Ala two invariant active site histidines, His-327 His-369, enzyme from Pseudomonas aeruginosa . Both mutants have lost activity but maintain ability reduce O 2 water. Nitrite is impaired because accumulation a catalytically inactive form,...
SUMMARY The mechanism of action praziquantel (PZQ), the drug choice against schistosomiasis, is still unclear. Since exposure schistosomes to associated with calcium influx and muscular contraction, channels have been suggested as target, although direct combination PZQ their subunits was never demonstrated. We report a hitherto unknown effect PZQ, namely inhibition nucleoside uptake, observed in living worms using radio-isotope labelled adenosine uridine. This clearly seen but absent...
Abstract Thioredoxin glutathione reductase (TGR) is a key flavoenzyme expressed by schistosomes that bridges two detoxification pathways crucial for the parasite survival in host's organism. In this article we report crystal structure (at 2.2 Å resolution) of TGR from Schistosoma mansoni (SmTGR), deleted last residues. The reveals peculiar architecture chimeric enzyme: small Glutaredoxin (Grx) domain at N‐terminus joined to large thioredoxin (TR) one via an extended complementary surface,...
MP4 (Hemospan) is a Hb-based oxygen therapeutic agent, based on polyethylene-glycol (PEG) conjugation to Hb, undergoing clinical trials as an carrier. This study describes the functional interaction between and carbon monoxide (CO), CO delivery effects of CO-MP4 myocardial infarct size following ischaemia reperfusion in rats.Kinetic measurements binding were used evaluate PEG modification Hb subunit structure/function calculate equilibrium constants. transport by was shown ligand (O2/CO)...
Abstract The determination of the function cells in zero-gravity conditions is a subject interest many different research fields. Due to their metabolic unicity, characterization behaviour erythrocytes maintained prolonged microgravity particular importance. Here, we used 3D-clinostat assess microgravity-induced modifications structure and these cells, by investigating how they translate peculiar mechanical stimuli into modifications, with potential clinical interest, biochemical pathways...
With the electro-driven import of rhodamine 123, we used single cell fluorescence microscopy to out contribution nitric oxide (NO) in controlling mitochondrial membrane potential expressed by (stationary growing) rhabdomyosarcoma and neuroblastoma cells culture. The experimental design computer-aided image analysis detected quantitated variations signals specific mitochondria. We observed that 1) two lines display changes dependent on energization states; 2) decreases after exposure a NO...
The S-conjugation rates of the free-reacting thiols present on each component rat hemoglobin with 5,5-dithio-bis(2,2-nitrobenzoic acid) (DTNB) have been studied under a variety conditions. On basis their reactivity DTNB (0.5 mM), three classes defined as follows: fast reacting (fHbSH), t1/2 <100 ms; slow (sHbSH), 30-50 s; and very (vsHbSH), 180-270 s. Under paraphysiological conditions, fHbSH (identified Cys-125beta(H3)) conjugates 100 times faster than glutathione approximately 4000 more...
Members of the FAD/NAD-linked reductase family are recognized as crucial targets in drug development for cancers, inflammatory disorders, and infectious diseases. However, individual FAD/NAD reductases difficult to inhibit a selective manner with off-target inhibition reducing usefulness identified compounds. Thioredoxin glutathione (TGR), high molecular weight thioredoxin reductase-like enzyme, has emerged promising target treatment schistosomiasis, parasitosis afflicting more than 200...