Roberto Contestabile

Pubblicazioni

Titolo Pubblicato in Anno
Identification of the pyridoxal 5′‐phosphate allosteric site in human pyridox(am)ine 5′‐phosphate oxidase PROTEIN SCIENCE 2024
Vitamin B6 deficiency cooperates with oncogenic Ras to induce malignant tumors in Drosophila CELL DEATH & DISEASE 2024
A gene-nutrient interaction between vitamin B6 and serine hydroxymethyltransferase (SHMT) affects genome integrity in Drosophila JOURNAL OF CELLULAR PHYSIOLOGY 2023
Structural insights into the DNA recognition mechanism by the bacterial transcription factor PdxR NUCLEIC ACIDS RESEARCH 2023
Functional and structural properties of pyridoxal reductase (PdxI) from Escherichia coli. A pivotal enzyme in the vitamin B6 salvage pathway THE FEBS JOURNAL 2023
Insights into the substrate specificity, structure, and dynamics of plant histidinol-phosphate aminotransferase (HISN6) PLANT PHYSIOLOGY AND BIOCHEMISTRY 2023
4'-Deoxypyridoxine disrupts vitamin B6 homeostasis in Escherichia coli K12 through combined inhibition of cumulative B6 uptake and PLP-dependent enzyme activity MICROBIOLOGY 2023
Structural insights into the DNA recognition mechanism by the bacterial transcription factor PdxR NUCLEIC ACIDS RESEARCH 2023
Cytosolic localization and in vitro assembly of human de novo thymidylate synthesis complex THE FEBS JOURNAL 2022
Thiamine-dependent regulation of mammalian brain pyridoxal kinase in vitro and in vivo JOURNAL OF NEUROCHEMISTRY 2022
Vitamin B6 rescues insulin resistance and glucose-induced DNA damage caused by reduced activity of Drosophila PI3K JOURNAL OF CELLULAR PHYSIOLOGY 2022
Riboregulation as a new player in the control of cellular metabolism: clues from the cryo-EM structure of serine hydroxymethyltransferase-RNA complex 2022
Arabidopsis thaliana serine hydroxymethyltransferases: functions, structures, and perspectives PLANT PHYSIOLOGY AND BIOCHEMISTRY 2022
Characterization of the Escherichia coli pyridoxal 5'-phosphate homeostasis protein (YggS): Role of lysine residues in PLP binding and protein stability PROTEIN SCIENCE 2022
Functional inactivation of drosophila GCK orthologs causes genomic instability and oxidative stress in a fly model of MODY-2 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 2021
Knowns and unknowns of vitamin B6 metabolism in escherichia coli ECOSAL PLUS 2021
Cytosolic localization and in vitro assembly of human de novo thymidylate synthesis complex 16th SIBBM Seminar Frontiers in Molecular Biology Frontiers in metabolic research Abstracts 2021
Identification and characterization of the pyridoxal 5'-phosphate allosteric site in Escherichia coli pyridoxine 5'-phosphate oxidase THE JOURNAL OF BIOLOGICAL CHEMISTRY 2021
A novel, easy assay method for human cysteine sulfinic acid decarboxylase LIFE 2021
Metformin is a pyridoxal-5′-phosphate (PLP)-competitive inhibitor of SHMT2 CANCERS 2021

ERC

  • LS1
  • LS1_2
  • LS1_4

KET

  • Life-science technologies & biotechnologies

Interessi di ricerca

My research activity has mainly concerned vitamin B6 metabolism, in humans and bacteria, and the mechanism, structure, regulation, metabolic role and inhibition of vitamin B6-dependent enzymes. At present, my interest is focused on the mechanisms of vitamin B6 homeostasis. On one side, I am investigating the transcriptional regulation of vitamin B6 biosynthesis and recycling pathways, focusing on bacterial organisms and the chimeric MocR proteins, which are PLP-binding transcriptional factors involved in the activation or repressor of vitamin B6 metabolism genes. On the other hand, I am studying the role of pyridoxal 5’-phosphate (PLP) carrier proteins, such as pyridoxine 5’-phosphate oxidase (PNPOx), pyridoxal kinase (PLK) and YggS, in controlling PLP homeostasis and delivery to apoenzymes in bacteria and humans. Besides, I am also committed to characterising the molecular basis of vitamin B6-dependend epilepsy, focusing my attention on missense mutations of human PNPOx. In this context, I am collaborating with clinicians to characterise novel mutations and correlate medical symptoms to the biochemical profile of patients. In recent years, I turned my attention to the role of serine hydroxymethyltransferase in the metabolic reprogramming of cancer cells, participating to two 3-year research programs funded by the Italian Association for Cancer Research (AIRC). My contribution to this field consisted in the study of the catalytic, structural and regulatory properties of both cytosolic and mitochondrial isoforms of the enzyme, the experimentation of novel inhibitors and the devise of in vivo activity assays. Lately, I have been involved in a project concerning the use of B6-enzymes as tools in the biosynthesis of unnatural amino acids and their intracellular incorporation in proteins and peptides.

Keywords

B vitamins
cell metabolism
enzyme
binding kinetics
Enzyme kinetics
homeostasis and regulation

© Università degli Studi di Roma "La Sapienza" - Piazzale Aldo Moro 5, 00185 Roma