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32 results on '"Parisi, Giacomo"'

6. Design of protein-binding peptides with controlled binding affinity: the case of SARS-CoV-2 receptor binding domain and angiotensin-converting enzyme 2 derived peptides

Author

Parisi, Giacomo, primary, Piacentini, Roberta, additional, Incocciati, Alessio, additional, Bonamore, Alessandra, additional, Macone, Alberto, additional, Rupert, Jakob, additional, Zacco, Elsa, additional, Miotto, Mattia, additional, Milanetti, Edoardo, additional, Tartaglia, Gian Gaetano, additional, Ruocco, Giancarlo, additional, Boffi, Alberto, additional, and Di Rienzo, Lorenzo, additional

Published
2024
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8. Effect of Salts on the Conformational Dynamics of the Cytochrome P450 OleP

Author

De Sciscio, Maria Laura, primary, Nardi, Alessandro Nicola, additional, Parisi, Giacomo, additional, Bulfaro, Giovanni, additional, Costanzo, Antonella, additional, Gugole, Elena, additional, Exertier, Cécile, additional, Freda, Ida, additional, Savino, Carmelinda, additional, Vallone, Beatrice, additional, Montemiglio, Linda Celeste, additional, and D’Abramo, Marco, additional

Published
2023
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10. Probing the Role of Murine Neuroglobin CDloop–D-Helix Unit in CO Ligand Binding and Structural Dynamics

Author

Exertier, Cécile, primary, Sebastiani, Federico, additional, Freda, Ida, additional, Gugole, Elena, additional, Cerutti, Gabriele, additional, Parisi, Giacomo, additional, Montemiglio, Linda Celeste, additional, Becucci, Maurizio, additional, Viappiani, Cristiano, additional, Bruno, Stefano, additional, Savino, Carmelinda, additional, Zamparelli, Carlotta, additional, Anselmi, Massimiliano, additional, Abbruzzetti, Stefania, additional, Smulevich, Giulietta, additional, and Vallone, Beatrice, additional

Published
2022
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13. Neuroglobin, clues to function and mechanism

Author

Exertier, Cécile, primary, Montemiglio, Linda Celeste, additional, Freda, Ida, additional, Gugole, Elena, additional, Parisi, Giacomo, additional, Savino, Carmelinda, additional, and Vallone, Beatrice, additional

Published
2022
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14. Point Mutations at a Key Site Alter the Cytochrome P450 OleP Structural Dynamics

Author

Montemiglio, Linda Celeste, primary, Gugole, Elena, additional, Freda, Ida, additional, Exertier, Cécile, additional, D’Auria, Lucia, additional, Chen, Cheng Giuseppe, additional, Nardi, Alessandro Nicola, additional, Cerutti, Gabriele, additional, Parisi, Giacomo, additional, D’Abramo, Marco, additional, Savino, Carmelinda, additional, and Vallone, Beatrice, additional

Published
2021
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15. Cytosolic localization and in vitro assembly of human de novo thymidylate synthesis complex

Author

Spizzichino, Sharon, primary, Boi, Dalila, additional, Boumis, Giovanna, additional, Lucchi, Roberta, additional, Liberati, Francesca Romana, additional, Capelli, Davide, additional, Montanari, Roberta, additional, Pochetti, Giorgio, additional, Piacentini, Roberta, additional, Parisi, Giacomo, additional, Paone, Alessio, additional, Rinaldo, Serena, additional, Contestabile, Roberto, additional, Tramonti, Angela, additional, Paiardini, Alessandro, additional, Giardina, Giorgio, additional, and Cutruzzolà, Francesca, additional

Published
2021
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16. Gating movements and ion permeation in HCN4 pacemaker channels

Author

Saponaro, Andrea, primary, Bauer, Daniel, additional, Giese, M. Hunter, additional, Swuec, Paolo, additional, Porro, Alessandro, additional, Gasparri, Federica, additional, Sharifzadeh, Atiyeh Sadat, additional, Chaves-Sanjuan, Antonio, additional, Alberio, Laura, additional, Parisi, Giacomo, additional, Cerutti, Gabriele, additional, Clarke, Oliver B., additional, Hamacher, Kay, additional, Colecraft, Henry M., additional, Mancia, Filippo, additional, Hendrickson, Wayne A., additional, Siegelbaum, Steven A., additional, DiFrancesco, Dario, additional, Bolognesi, Martino, additional, Thiel, Gerhard, additional, Santoro, Bina, additional, and Moroni, Anna, additional

Published
2021
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20. Cytosolic localization and in vitro assembly of human de novo thymidylate synthesis complex.

Author

Spizzichino, Sharon, Boi, Dalila, Boumis, Giovanna, Lucchi, Roberta, Liberati, Francesca Romana, Capelli, Davide, Montanari, Roberta, Pochetti, Giorgio, Piacentini, Roberta, Parisi, Giacomo, Paone, Alessio, Rinaldo, Serena, Contestabile, Roberto, Tramonti, Angela, Paiardini, Alessandro, Giardina, Giorgio, and Cutruzzolà, Francesca

Subjects
THYMIDYLATE synthase, TETRAHYDROFOLATE dehydrogenase, CARCINOMA in situ, PROTEIN-protein interactions, CANCER cells, DIHYDROPYRIMIDINE dehydrogenase
Abstract

De novo thymidylate synthesis is a crucial pathway for normal and cancer cells. Deoxythymidine monophosphate (dTMP) is synthesized by the combined action of three enzymes: serine hydroxymethyltransferase (SHMT1), dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS), with the latter two being targets of widely used chemotherapeutics such as antifolates and 5‐fluorouracil. These proteins translocate to the nucleus after SUMOylation and are suggested to assemble in this compartment into the thymidylate synthesis complex. We report the intracellular dynamics of the complex in cancer cells by an in situ proximity ligation assay, showing that it is also detected in the cytoplasm. This result indicates that the role of the thymidylate synthesis complex assembly may go beyond dTMP synthesis. We have successfully assembled the dTMP synthesis complex in vitro, employing tetrameric SHMT1 and a bifunctional chimeric enzyme comprising human thymidylate synthase and dihydrofolate reductase. We show that the SHMT1 tetrameric state is required for efficient complex assembly, indicating that this aggregation state is evolutionarily selected in eukaryotes to optimize protein–protein interactions. Lastly, our results regarding the activity of the complete thymidylate cycle in vitro may provide a useful tool with respect to developing drugs targeting the entire complex instead of the individual components. [ABSTRACT FROM AUTHOR]

Published
2022
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23. Gating Movements and Ion Permeation in HCN4 Pacemaker Channels

Author

Saponaro, Andrea, primary, Bauer, Daniel, additional, Giese, M. Hunter, additional, Swuec, Paolo, additional, Porro, Alessandro, additional, Gasparri, Federica, additional, Sharifzadeh, Atiyeh Sadat, additional, Chaves-Sanjuan, Antonio, additional, Alberio, Laura, additional, Parisi, Giacomo, additional, Cerutti, Gabriele, additional, Clarke, Oliver, additional, Hamacher, Kay, additional, Colecraft, Henry M., additional, Mancia, Filippo, additional, Hendrickson, Wayne A., additional, Siegelbaum, Steven A., additional, DiFrancesco, Dario, additional, Bolognesi, Martino, additional, Thiel, Gerhard, additional, Santoro, Bina, additional, and Moroni, Anna, additional

Published
2020
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25. 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

Author

Scaglione, Antonella, Fullone, Maria Rosaria, Montemiglio, Linda Celeste, Parisi, Giacomo, Zamparelli, Carlotta, Vallone, Beatrice, Savino, Carmelinda, and Grgurina, Ingeborg

Subjects
0301 basic medicine, Models, Molecular, Protein Conformation, alpha-Helical, Threonine, Stereochemistry, Adenylate kinase, Gene Expression, Crystal structure, Crystallography, X-Ray, Biochemistry, Streptomyces, Substrate Specificity, 03 medical and health sciences, chemistry.chemical_compound, Adenosine Triphosphate, Biosynthesis, Bacterial Proteins, adenylation domain, crystallography, kinetic analysis, nonribosomal code, substrate specificity, biochemistry, molecular biology, cell biology, Escherichia coli, heterocyclic compounds, Protein Interaction Domains and Motifs, Amino Acid Sequence, Cloning, Molecular, Peptide Synthases, Molecular Biology, Adenylylation, chemistry.chemical_classification, Binding Sites, 030102 biochemistry & molecular biology, biology, Sequence Homology, Amino Acid, Active site, Substrate (chemistry), Cell Biology, biology.organism_classification, Recombinant Proteins, Kinetics, 030104 developmental biology, Enzyme, chemistry, biology.protein, Protein Conformation, beta-Strand, Sequence Alignment, Protein Binding
Abstract

We determined the crystal structure of Thr1, the self-standing adenylation domain involved in the nonribosomal-like biosynthesis of free 4-chlorothreonine in Streptomyces sp. OH-5093. Thr1 shows two monomers in the crystallographic asymmetric unit with different relative orientations of the C- and N-terminal subdomains both in the presence of substrates and in the unliganded form. Cocrystallization with substrates, adenosine 5?-triphosphate and l-threonine, yielded one monomer containing the two substrates and the other in complex with l-threonine adenylate, locked in a postadenylation state. Steady-state kinetics showed that Thr1 activates l-Thr and its stereoisomers, as well as d-Ala, l- and d-Ser, albeit with lower efficiency. Modeling of these substrates in the active site highlighted the molecular bases of substrate discrimination. This work provides the first crystal structure of a threonine-activating adenylation enzyme, a contribution to the studies on conformational rearrangement in adenylation domains and on substrate recognition in nonribosomal biosynthesis. Database: Structural data are available in the Protein Data Bank under the accession number 5N9W and 5N9X.

Published
2016

26. Substrate‐induced conformational change in cytochrome P450 OleP

Author

Parisi, Giacomo, primary, Montemiglio, Linda Celeste, additional, Giuffrè, Alessandro, additional, Macone, Alberto, additional, Scaglione, Antonella, additional, Cerutti, Gabriele, additional, Exertier, Cécile, additional, Savino, Carmelinda, additional, and Vallone, Beatrice, additional

Published
2018
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27. Effects of Y361‐auto‐phosphorylation on structural plasticity of the HIPK2 kinase domain

Author

Scaglione, Antonella, primary, Monteonofrio, Laura, additional, Parisi, Giacomo, additional, Cecchetti, Cristina, additional, Siepi, Francesca, additional, Rinaldo, Cinzia, additional, Giorgi, Alessandra, additional, Verzili, Daniela, additional, Zamparelli, Carlotta, additional, Savino, Carmelinda, additional, Soddu, Silvia, additional, Vallone, Beatrice, additional, and Montemiglio, Linda Celeste, additional

Published
2017
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29. Substrate-induced conformational change in cytochrome P450 OleP.

Author

Parisi, Giacomo, Montemiglio, Linda Celeste, Giuffrè, Alessandro, Macone, Alberto, Scaglione, Antonella, Cerutti, Gabriele, Exertier, Cécile, Savino, Carmelinda, and Vallone, Beatrice

Abstract

The regulation of cytochrome P450 activity is often achieved by structural transitions induced by substrate binding. We describe the conformational transition experienced upon binding by the P450 OleP, an epoxygenase involved in oleandomycin biosynthesis. OleP bound to the substrate analog 6DEB crystallized in 2 forms: one with an ensemble of open and closed conformations in the asymmetric unit and another with only the closed conformation. Characterization of OleP-6DEB binding kinetics, also using the P450 inhibitor clotrimazole, unveiled a complex binding mechanism that involves slow conformational rearrangement with the accumulation of a spectroscopically detectable intermediate where 6DEB is bound to open OleP. Data reported herein provide structural snapshots of key precatalytic steps in the OleP reaction and explain how structural rearrangements induced by substrate binding regulate activity. [ABSTRACT FROM AUTHOR]

Published
2019
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31. Point Mutations at a Key Site Alter the Cytochrome P450 OleP Structural Dynamics.

Author

Montemiglio, Linda Celeste, Gugole, Elena, Freda, Ida, Exertier, Cécile, D'Auria, Lucia, Chen, Cheng Giuseppe, Nardi, Alessandro Nicola, Cerutti, Gabriele, Parisi, Giacomo, D'Abramo, Marco, Savino, Carmelinda, and Vallone, Beatrice

Subjects
CYTOCHROME P-450, STRUCTURAL dynamics, CYTOCHROME c, CRYSTAL structure, DYNAMIC simulation, X-ray crystallography
Abstract

Substrate binding to the cytochrome P450 OleP is coupled to a large open-to-closed transition that remodels the active site, minimizing its exposure to the external solvent. When the aglycone substrate binds, a small empty cavity is formed between the I and G helices, the BC loop, and the substrate itself, where solvent molecules accumulate mediating substrate-enzyme interactions. Herein, we analyzed the role of this cavity in substrate binding to OleP by producing three mutants (E89Y, G92W, and S240Y) to decrease its volume. The crystal structures of the OleP mutants in the closed state bound to the aglycone 6DEB showed that G92W and S240Y occupied the cavity, providing additional contact points with the substrate. Conversely, mutation E89Y induces a flipped-out conformation of this amino acid side chain, that points towards the bulk, increasing the empty volume. Equilibrium titrations and molecular dynamic simulations indicate that the presence of a bulky residue within the cavity impacts the binding properties of the enzyme, perturbing the conformational space explored by the complexes. Our data highlight the relevance of this region in OleP substrate binding and suggest that it represents a key substrate-protein contact site to consider in the perspective of redirecting its activity towards alternative compounds. [ABSTRACT FROM AUTHOR]

Published
2022
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32. Structuring lipid nanoparticles, DNA, and protein corona into stealth bionanoarchitectures for in vivo gene delivery.

Author

Renzi S, Digiacomo L, Pozzi D, Quagliarini E, Vulpis E, Giuli MV, Mancusi A, Natiello B, Pignataro MG, Canettieri G, Di Magno L, Pesce L, De Lorenzi V, Ghignoli S, Loconte L, Montone CM, Laura Capriotti A, Laganà A, Nicoletti C, Amenitsch H, Rossi M, Mura F, Parisi G, Cardarelli F, Zingoni A, Checquolo S, and Caracciolo G

Subjects
Animals, Humans, Mice, Lipids chemistry, SARS-CoV-2 genetics, Transfection methods, Polyethylene Glycols chemistry, Female, Particle Size, Liposomes, Nanoparticles chemistry, Protein Corona chemistry, Protein Corona metabolism, DNA chemistry, DNA metabolism, Gene Transfer Techniques, Genetic Therapy methods, COVID-19 virology
Abstract

Lipid nanoparticles (LNPs) play a crucial role in addressing genetic disorders, and cancer, and combating pandemics such as COVID-19 and its variants. Yet, the ability of LNPs to effectively encapsulate large-size DNA molecules remains elusive. This is a significant limitation, as the successful delivery of large-size DNA holds immense potential for gene therapy. To address this gap, the present study focuses on the design of PEGylated LNPs, incorporating large-sized DNA, departing from traditional RNA and ionizable lipids. The resultant LNPs demonstrate a unique particle morphology. These particles were further engineered with a DNA coating and plasma proteins. This multicomponent bionanoconstruct exhibits enhanced transfection efficiency and safety in controlled laboratory settings and improved immune system evasion in in vivo tests. These findings provide valuable insights for the design and development of bionanoarchitectures for large-size DNA delivery, opening new avenues for transformative gene therapies., (© 2024. The Author(s).)

Published
2024
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