Enzymes Modulations:

their key role in Health and Diseases

Control of biological systems

Ligand-macromolecule interactions are of fundamental importance in the control of biological processes.

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Simple but not simpler

the structural reasons of enzyme functional modulation

Enzyme modulators in Non Celiac Gluten Sensitivity

Wheat amylase/trypsin bi-functional inhibitors (ATIs) are protein stimulators of innate immune response, with a recently established role in promoting both gastrointestinal and extra-gastrointestinal inflammatory syndromes. These proteins have been reported to trigger downstream intestinal inflammation upon activation of TLR4, a member of the Toll-like family of proteins that activates signalling pathways and induces the expression of immune and pro-inflammatory genes. Our research group demonstrated the ability of ATI to directly interact with TLR4 with nanomolar affinity (reference)

Autoantibodies in Systemic sclerosis detection

Systemic sclerosis (SSc) is a chronic autoimmune disease of the connective tissue. The variety and clinical relevance of autoantibodies in SSc patients have been extensively studied, eventually identifying agonistic autoantibodies targeting the platelet-derived growth factor receptor alpha (PDGFRα), and representing potential biomarkers for SSc. We developed a resonant mirror biosensor to characterize the binding between surface-blocked PDGFRα and PDGFRα-specific recombinant human monoclonal autoantibodies (mAbs) produced by SSc B cells, and detect/quantify serum autoimmune IgG with binding characteristics similar to the mAbs (reference)

Mangiferin blocks proliferation and induces apoptosis of breast cancer cells

Mangiferin is a natural xanthone glycoside with therapeutic potential. Its cytotoxic properties were explored in a human cell model of breast adenocarcinoma. The results supported the multi-target nature of mangiferin action, as the inhibition of three enzymatic systems, namely HMG-CoA reductase, the proteasome and plasmin. Globally, mangiferin was able to selectively block breast cancer cell growth by inducing apoptosis and by arresting cell proliferation through a combined action. (reference)

Environmental pollutants as ligands of the liver X receptor alpha

Liver X receptor is a ligand-activated transcription factor, which is mainly involved in cholesterol homeostasis, bile acid and triglycerides metabolism, and, as recently discovered, in the glucose metabolism by direct regulation of liver glucokinase. Phthalates, organophosphates and fibrates classes were tested as ligands/modulators of human liver X receptor, using SPR biosensor ad docking analysis. (reference)

Perspective Research projects

Fno (EC 1.5.1.40) inhibition in Irritable Bowel Disease Syndrome

The reduced F420 coenzyme (a 7,8-didemethyl-8-hydroxy-5- deazariboflavin-5′-phosphoryllactyl(glutamyl)nglutamate) is used in the methanogenesis pathway in Methanogens. The catabolic pathways of methanogens reduce F420 and ferredoxin, but not nicotinamides. In order to generate NADPH for biosynthetic processes, methanogens instead transfer electrons from F420H2 to NADP.

This process depends on F420H2: NADP oxidoreductase (Fno, EC 1.5.1.40), a physiologically-reversible enzyme that primarily acts as an F420H2-dependent NADP reductase in Methanogens. Our research groups is focussed in searching for specific inhibitors of Fno.