A5070703952- Enzyme Structure and Function
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Biochemical and Molecular Research
- Bacterial Genetics and Biotechnology
- Cancer, Hypoxia, and Metabolism
- Folate and B Vitamins Research
- ATP Synthase and ATPases Research
- RNA and protein synthesis mechanisms
- Aldose Reductase and Taurine
- Trace Elements in Health
- Protein Structure and Dynamics
- Bacteriophages and microbial interactions
- Electron Spin Resonance Studies
- Retinoids in leukemia and cellular processes
- DNA Repair Mechanisms
- Chemotherapy-induced organ toxicity mitigation
- RNA Research and Splicing
- Microbial Metabolic Engineering and Bioproduction
- Neonatal Health and Biochemistry
- Plant biochemistry and biosynthesis
- Metal-Catalyzed Oxygenation Mechanisms
- Probiotics and Fermented Foods
- Heme Oxygenase-1 and Carbon Monoxide
- Prenatal Substance Exposure Effects
Institute of Molecular Biology and Pathology
2020-2024
National Research Council
2023
Istituto Pasteur
2018-2022
Sapienza University of Rome
2018-2022
University of Rome Tor Vergata
2019
Serine hydroxymethyltransferase (SHMT) catalyzes the reversible conversion of l-serine and tetrahydrofolate into glycine 5,10-methylenetetrahydrofolate. This enzyme, which plays a pivotal role in one-carbon metabolism, is involved cancer metabolic reprogramming recognized target chemotherapy intervention. In humans, two isoforms enzyme exist, are commonly termed cytosolic SHMT1 mitochondrial SHMT2. Considerable attention has been paid to structural, mechanistic, features these isozymes. On...
Abstract Defects of vitamin B 6 metabolism are responsible for severe neurological disorders, such as pyridoxamine 5′-phosphate oxidase deficiency (PNPOD; OMIM: 610090), an autosomal recessive inborn error that usually manifests with neonatal-onset seizures and subsequent encephalopathy. At present, 27 pathogenic mutations the gene encoding human PNPO known, 13 which homozygous missense mutations; however, only 3 them have been characterised respect to molecular functional properties variant...
Abstract The pyridoxal 5′‐phosphate (PLP) homeostasis protein (PLPHP) is a ubiquitous member of the COG0325 family with apparently no catalytic activity. Although actual cellular role this unknown, it has been observed that mutations PLPHP encoding gene affect activity PLP‐dependent enzymes, B 6 vitamers and amino acid levels. Here we report detailed characterization Escherichia coli ortholog (YggS) respect to its PLP binding transfer properties, stability, structure. YggS binds very tightly...
Abstract Adequate levels of pyridoxal 5′‐phosphate (PLP), the catalytically active form vitamin B 6 , and its proper distribution in body are essential for human health. The PLP recycling pathway plays a crucial role these processes defects cause severe neurological diseases. enzyme pyridox(am)ine oxidase (PNPO), whose catalytic action yields PLP, is one key players this pathway. Mutations gene encoding PNPO responsible neonatal epilepsy. Recently, has also been described as potential target...
Plants, algae and most bacteria synthesize 5-aminolevulinic acid (ALA), the universal precursor of tetrapyrroles such as heme, chlorophyll coenzyme B12, by a two-step transformation involving NADPH-dependent glutamyl-tRNA reductase (HemA), which reduces tRNA-bound glutamate to glutamate-1-semialdehyde (GSA), pyridoxamine 5'-phosphate-dependent glutamate-1-semialdehyde-2,1-aminomutase (HemL), responsible for isomerization GSA into ALA. Since is very unstable compound at pH values around...
Abstract In eukaryotes, pyridoxal kinase (PDXK) acts in vitamin B 6 salvage pathway to produce 5′-phosphate (PLP), the active form of vitamin, which is implicated numerous crucial metabolic reactions. Drosophila , mutations dPdxk gene cause chromosome aberrations (CABs) and increase glucose content larval hemolymph. Both phenotypes are rescued by expression wild type human PDXK counterpart. Here we expressed, 1 mutant flies, four variants: three (D87H, V128I H246Q) listed databases, one...
In Escherichia coli, the synthesis of pyridoxal 5'-phosphate (PLP), catalytically active form vitamin B6, takes place through so-called deoxyxylulose 5-phosphate-dependent pathway, whose last step is pyridoxine (PNP) oxidation to PLP, catalyzed by FMN-dependent enzyme PNP oxidase (PNPOx). This plays a pivotal role in controlling intracellular homeostasis and bioavailability PLP. PNPOx has been proposed undergo product inhibition resulting from PLP binding at site. also reported bind tightly...
Pyridoxal 5'-phosphate (PLP), the catalytically active form of vitamin B6, plays a pivotal role in metabolism as an enzyme cofactor. PLP is very reactive molecule and can be toxic unless its intracellular concentration finely regulated. In Escherichia coli, formation catalyzed by pyridoxine oxidase (PNPO), homodimeric FMN-dependent that responsible for last step biosynthesis also involved salvage pathway. We have recently observed E. coli PNPO undergoes allosteric feedback inhibition PLP,...
Bacillus subtilis is able to use γ-aminobutyric acid (GABA) found in the soil as carbon and nitrogen source, through action of GABA aminotransferase (GabT) succinic semialdehyde dehydrogenase (GabD). acts molecular effector transcriptional activation gabTD operon by GabR. GabR most studied member MocR family prokaryotic pyridoxal 5'-phosphate (PLP)-dependent regulators, yet crucial aspects its mechanism are unknown. binds promoter, but transcription activated only when present. Here, we...
Pyridoxine 4‐dehydrogenase (PdxI), a NADPH‐dependent pyridoxal reductase, is one of the key players in Escherichia coli 5′‐phosphate (PLP) salvage pathway. This enzyme, which catalyses reduction into pyridoxine, causes to be converted PLP via formation pyridoxine and phosphate. The structural functional properties PdxI were hitherto unknown, preventing rational explanation how why this longer, detoured pathway occurs, given that, E. , two kinases (PdxK PdxY) exist that could convert directly...
Specificity in protein-DNA recognition arises from the synergy of several factors that stem structural and chemical signatures encoded within targeted DNA molecule. Here, we deciphered nature interactions driving binding by bacterial transcription factor PdxR, a member MocR family responsible for regulation pyridoxal 5'-phosphate (PLP) biosynthesis. Single particle cryo-EM performed on PLP-PdxR bound to its target enabled isolation three conformers complex, which may be considered as...
Cysteine sulfinic acid decarboxylase catalyzes the last step of taurine biosynthesis in mammals, and belongs to fold type I superfamily pyridoxal-5'-phosphate (PLP)-dependent enzymes. Taurine (2-aminoethanesulfonic acid) is most abundant free amino animal tissues; it highly present liver, kidney, muscle, brain, plays numerous biological physiological roles. Despite importance human health, cysteine has been poorly characterized at biochemical level, although its three-dimensional structure...
Several variants of the enzyme pyridox(am)ine 5'-phosphate oxidase (PNPO), responsible for a rare form vitamin B6-dependent neonatal epileptic encephalopathy known as PNPO deficiency (PNPOD), have been reported. However, only few them characterised with respect to their structural and functional properties, despite fact that knowledge how affect may clarify disease mechanism improve treatment. Here, we report characterisation catalytic, allosteric properties recombinantly expressed D33V,...
Pyridoxal 5′‐phosphate (PLP), the catalytically active form of vitamin B 6 , acts as a cofactor in many metabolic processes. In humans, PLP is produced reactions catalysed by pyridox(am)ine oxidase (PNPO) and pyridoxal kinase (PDXK). Both PNPO PDXK are involved cancer progression tumours. The silencing encoding genes determines strong reduction tumour size neoplastic cell invasiveness models acute myeloid leukaemia (in case PDXK) ovarian breast PNPO). present work, we demonstrate that...
Abstract The pyridoxal 5′‐phosphate binding protein (PLP‐BP) is believed to play a crucial role in PLP homeostasis, which may explain why it found living organisms from all kingdoms. Escherichia coli YggS the most studied homolog, but human PLP‐BP has also attracted much attention because variants of this are responsible for severe form B 6 ‐responsive neonatal epilepsy. Yet, how involved and thus what its actual function cellular metabolism, entirely unknown. present study shows that binds...