|Effect of Salts on the Conformational Dynamics of the Cytochrome P450 OleP||MOLECULES||2023|
|Point mutations at a key site alter the cytochrome P450 oleP structural dynamics||BIOMOLECULES||2022|
|Neuroglobin, clues to function and mechanism||MOLECULAR ASPECTS OF MEDICINE||2022|
|Probing the role of murine neuroglobin CDloop-D-Helix unit in CO ligand binding and structural dynamics||ACS CHEMICAL BIOLOGY||2022|
|ALS2-Related Motor Neuron Diseases: From Symptoms to Molecules||BIOLOGY||2022|
|Crystal structure and functional characterization of an oligosaccharide dehydrogenase from Pycnoporus cinnabarinus provides insights into fungal breakdown of lignocellulose||BIOTECHNOLOGY FOR BIOFUELS||2021|
|The nuts and bolts of SARS-CoV-2 spike receptor-binding domain heterologous expression||BIOMOLECULES||2021|
|Lack of orientation selectivity of the heme insertion in murine neuroglobin revealed by resonance Raman spectroscopy||THE FEBS JOURNAL||2020|
|Dissecting the cytochrome P450 OleP substrate specificity: evidence for a preferential substrate||BIOMOLECULES||2020|
|Substrate-induced conformational change in cytochrome P450 OleP||THE FASEB JOURNAL||2019|
|Cryo-EM structure of the human ferritin–transferrin receptor 1 complex||NATURE COMMUNICATIONS||2019|
|Proximal and distal control for ligand binding in neuroglobin: role of the CD loop and evidence for His64 gating||SCIENTIFIC REPORTS||2019|
|Ligand pathways in neuroglobin revealed by low-temperature photodissociation and docking experiments||IUCRJ||2019|
|Effects of Y361-auto-phosphorylation on structural plasticity of the HIPK2 kinase domain||PROTEIN SCIENCE||2018|
|Humanized archaeal ferritin as a tool for cell targeted delivery||NANOSCALE||2017|
|Subcellular localization of the five members of the human steroid 5α-reductase family||BIOCHIMIE OPEN||2017|
|Determinants of neuroglobin plasticity highlighted by joint coarse-grained simulations and high pressure crystallography||SCIENTIFIC REPORTS||2017|
|Structure of the adenylation domain thr1 involved in the biosynthesis of 4-chlorothreonine in Streptomyces sp. OH-5093 - protein flexibility and molecular bases of substrate specificity||THE FEBS JOURNAL||2017|
|Mapping hydrophobic tunnels and cavities in neuroglobin with noble gas under pressure||BIOPHYSICAL JOURNAL||2017|
|Functional analysis and crystallographic structure of clotrimazole bound olep, a cytochrome p450 epoxidase from Streptomyces antibioticus involved in oleandomycin biosynthesis||BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS||2016|
Main research fields: structural biology and biochemistry.
The mechanism of action of proteins was investigated by using protein crystallography and biochemical characterization. This included the structure-function relationship of enzymes and transporters as well as their role within signalling networks that involves protein-protein recognition and complex formation.
The knowledge of the molecular mechanism exploited by proteins to carry out their function and involved in pathological processes is the starting point to design novel, targeted therapeutic strategies. In this contest, the main endeavour has been the determination of protein structures by protein crystallography and, more recently by single particle cryo-electron microscopy. Protein biochemical and biophysical characterization was carried out using a wide array of methods (kinetics, protein engineering, spectroscopy).
The most relevant results have been:
1. The study by single particle cryo-elecron microscopy of engineered ferritins and of the complex between human ferritin and the CD71 receptor.
2. Structural and functional analysis of enzymes involved in antibiotic biosynthesis, that led to the determination of the structure of a new type of monooxygenase involved in the biosynthesis of aromatic polyketids and of P450 cytochromes involved in the biosynthesis of macrolide antibiotics, erythromycin and oleandomycin.
3. The determination of the structure of murine neuroglobin in different ligation states where a novel mechanism for ligand affinity regulation (heme sliding) was described and the characterization of its reactivity towards nitric oxide.
4. The study by time-resolved crystallography/wide angle X-ray scattering and molecular dynamics of myoglobin, hemoglobin and neuroglobin structural dynamics, that contributed to the to the description by direct detection of the pathway of ligands within the protein matrix and to the unveiling of a complex sub-nanosecond structural dynamics triggered by ligand dissociation.
Ongoing projects: integrative structural biology, biochemical characterization and engineering of i) ferritins as theranostics nanoparticles ii) Steroid 5-a dihydrogenases as oncotargets and pivotal membrane enzymes in neurosteroid biosynthesis iii) interaction between the oncosuppressor HIPK2 kinase and its target, p53.
Ongoing research is focussed on the structure-function relationship of proteins involved in human pathologies, also for theranostics desigs:
1. Complex of plasma proteins with their receptors (haptoglobin, ferritin and LDL-receptor related protein)
2. Steroid 5-a dehydrogenase membrane enzymes
3. Alsin ALS-2 GEF in collaboration with the Politecnico of Turin, with the support of a Telethon Grant
4. SARS-COV-2 antibodies for diagnostics and therapy in collaboration with Takis Biotech with the support of grants from Regione Lazio.
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