A5024127044- Porphyrin Metabolism and Disorders
- Kidney Stones and Urolithiasis Treatments
- Metabolism and Genetic Disorders
- Folate and B Vitamins Research
- Biomedical Research and Pathophysiology
- Enzyme Structure and Function
- Mitochondrial Function and Pathology
- Amino Acid Enzymes and Metabolism
- Cancer, Hypoxia, and Metabolism
- Trace Elements in Health
- Peroxisome Proliferator-Activated Receptors
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Biochemical and Molecular Research
- ATP Synthase and ATPases Research
- Cassava research and cyanide
- Genetic Neurodegenerative Diseases
- Plant pathogens and resistance mechanisms
- Tissue Engineering and Regenerative Medicine
- Diet and metabolism studies
- Autophagy in Disease and Therapy
- Microbial metabolism and enzyme function
- Photoreceptor and optogenetics research
- Gout, Hyperuricemia, Uric Acid
- Eicosanoids and Hypertension Pharmacology
University of Verona
2011-2021
Tumor dormancy is a poorly understood stage in cancer progression characterized by mitotic cycle arrest G0/G1 phase and low metabolism. The cells survive quiescent state wait for appropriate environmental conditions to begin proliferation again giving rise metastasis. Despite their key role development metastasis, the knowledge about biology origin still very limited due poorness of established vitro models that faithfully recapitulated tumor dormancy. Using at least three cycles 1% O2...
G41 is an interfacial residue located within the alpha-helix 34-42 of alanine:glyoxylate aminotransferase (AGT). Its mutations on major (AGT-Ma) or minor (AGT-Mi) allele give rise to variants G41R-Ma, G41R-Mi, and G41V-Ma causing hyperoxaluria type 1. Impairment dimerization in these has been suggested be responsible for immunoreactivity deficiency, intraperoxisomal aggregation, sensitivity proteasomal degradation. However, no experimental evidence supports this view. Here we report that...
Vitamin B6 in the form of pyridoxine (PN) is one most widespread pharmacological therapies for inherited diseases involving pyridoxal phosphate (PLP)-dependent enzymes, including primary hyperoxaluria type I (PH1). PH1 caused by a deficiency liver-peroxisomal alanine: glyoxylate aminotransferase (AGT), which allows oxidation to oxalate leading deposition insoluble calcium kidney. Only minority patients, mostly bearing F152I and G170R mutations, respond PN, only treatment currently available....
The TP53 tumor suppressor gene is the most frequently altered in tumors and mutant p53 gain-of-function isoforms actively promote cancer malignancy.A panel of wild-type cell lines different tissues, including pancreas, breast, skin, lung were used, as well chronic lymphocytic leukemia (CLL) patients with status. effects evaluated by confocal microscopy, reactive oxygen species production assay, immunoblotting, quantitative reverse transcription polymerase chain reaction after cellular...
Abstract Most pathogenic missense mutations cause specific molecular phenotypes through protein destabilization. However, how destabilization is manifested as a given phenotype not well understood. We develop here structural and energetic approach to describe mutational effects on traits such function, regulation, stability, subcellular targeting or aggregation propensity. This tested using large-scale experimental perturbation analyses in over thirty three different proteins...
Abstract Low plasma concentrations of L-homoarginine are associated with an increased risk cardiovascular events, while homoarginine supplementation is protective in animal models metabolic syndrome and stroke. Catabolism still poorly understood. Based on the recent findings from a Genome Wide Association Study we hypothesized that can be metabolized by alanine:glyoxylate aminotransferase 2 (AGXT2). We purified human AGXT2 tissues transgenic mice demonstrated its ability to metabolize...
Guanylate Cyclase-Activating Protein 1 (GCAP1) regulates the enzymatic activity of photoreceptor guanylate cyclases (GC), leading to inhibition or activation cyclic guanosine monophosphate (cGMP) synthesis depending on its Ca2+- Mg2+-loaded state. By genetically screening a family patients diagnosed with cone-rod dystrophy, we identified novel missense mutation autosomal dominant inheritance pattern (c.332A>T; p.(Glu111Val); E111V from now on) in GUCA1A gene coding for GCAP1. We performed...
Dopa or aromatic amino acid decarboxylase (DDC, AADC) is a pyridoxal 5′-phosphate-dependent enzyme that catalyses the production of neurotransmitters dopamine and serotonin. Among so far identified mutations associated with AADC deficiency, an inherited rare neurometabolic disease, S250F mutation most frequent one. Here, for first time, molecular basis deficit variant was investigated both in vitro cellular systems. Ser250 not essential catalytic activity enzyme. However, its to Phe causes...
The substitution of Ser187, a residue located far from the active site human liver peroxisomal alanine:glyoxylate aminotransferase (AGT), by Phe gives rise to variant associated with primary hyperoxaluria type I. Unexpectedly, previous studies revealed that recombinant form S187F exhibits remarkable loss catalytic activity, an increased pyridoxal 5'-phosphate (PLP) binding affinity and different coenzyme mode compared normal AGT. To shed light on structural elements responsible for these...
The rare disease Primary Hyperoxaluria Type I (PH1) results from the deficit of liver peroxisomal alanine:glyoxylate aminotransferase (AGT), as a consequence inherited mutations on AGXT gene frequently leading to protein misfolding. Pharmacological chaperone (PC) therapy is newly developed approach for misfolding diseases based use small molecule ligands able promote correct folding mutant enzyme. In this report, we describe interaction amino-oxyacetic acid (AOA) with recombinant purified...
Primary Hyperoxaluria type I (PH1) is a rare disease due to the deficit of peroxisomal alanine:glyoxylate aminotransferase (AGT), homodimeric pyridoxal-5′-phosphate (PLP) enzyme present in humans as major (Ma) and minor (Mi) allele. PH1-causing mutations are mostly missense identified both homozygous compound heterozygous patients. Until now, pathogenesis PH1 has been only studied by approaches mimicking patients, whereas molecular aspects genotype-enzymatic-clinical phenotype relationship...
Abstract Oxalate decarboxylase (OxDC) from Bacillus subtilis is a Mn‐dependent hexameric enzyme that converts oxalate to carbon dioxide and formate. OxDC has greatly attracted the interest of scientific community, mainly due its biotechnological medical applications in particular for treatment hyperoxaluria, group pathologic conditions caused by accumulation. The an acidic optimum pH, but most involve processes occurring at neutral pH. Nevertheless, detailed biochemical characterization pH...
Human Dopa decarboxylase (hDDC), a pyridoxal 5′-phosphate (PLP) enzyme, displays maxima at 420 and 335 nm emits fluorescence 384 504 upon excitation when excited nm. Absorbance titrations of hDDC-bound coenzyme identify single<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:msub><mml:mtext>pK</mml:mtext><mml:mrow><mml:mtext>spec</mml:mtext></mml:mrow></mml:msub></mml:mrow></mml:math>of ~7.2. This<mml:math...