Giovanni Minervini

@article{DelConte2024W306,

title = {RING 4.0: Faster residue interaction networks with novel interaction types across over 35,000 different chemical structures},

author = { Alessio Del Conte and Giorgia F Camagni and Damiano Clementel and Giovanni Minervini and Alexander Miguel Monzon and Carlo Ferrari and Damiano Piovesan and Silvio C. E Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85197788039\&doi=10.1093%2fnar%2fgkae337\&partnerID=40\&md5=bca70d16fbb39f5466a3957673ef9eef},

doi = {10.1093/nar/gkae337},

issn = {03051048},

year  = {2024},

date = {2024-01-01},

abstract = {Residue interaction networks (RINs) are a valuable approach for representing contacts in protein structures. RINs have been widely used in various research areas, including the analysis of mutation effects, domain-domain communication, catalytic activity, and molecular dynamics simulations. The RING server is a powerful tool to calculate non-covalent molecular interactions based on geometrical parameters, providing high-quality and reliable results. Here, we introduce RING 4.0, which includes significant enhancements for identifying both covalent and non-covalent bonds in protein structures. It now encompasses seven different interaction types, with the addition of π-hydrogen, halogen bonds and metal ion coordination sites. The definitions of all available bond types have also been refined and RING can now process the complete PDB chemical component dictionary (over 35000 different molecules) which provides atom names and covalent connectivity information for all known ligands. Optimization of the software has improved execution time by an order of magnitude. The RING web server has been redesigned to provide a more engaging and interactive user experience, incorporating new visualization tools. Users can now visualize all types of interactions simultaneously in the structure viewer and network component. The web server, including extensive help and tutorials, is available from URL: https://ring.biocomputingup.it/. © 2024 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 5; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Inciardi2024,

title = {Catechol-induced covalent modifications modulate the aggregation tendency of α-synuclein: An in-solution and in-silico study},

author = { Ilenia Inciardi and Elena Rizzotto and Francesco Gregoris and Benedetta Fongaro and Alice Sosic and Giovanni Minervini and Patrizia Polverino de Laureto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85194767977\&doi=10.1002%2fbiof.2086\&partnerID=40\&md5=aff1210a238a2481081bf8c704ba8ef5},

doi = {10.1002/biof.2086},

issn = {09516433},

year  = {2024},

date = {2024-01-01},

abstract = {Parkinson's disease (PD) stands as a challenging neurodegenerative condition characterized by the emergence of Lewy Bodies (LBs), intracellular inclusions within dopaminergic neurons. These LBs harbor various proteins, prominently including α-Synuclein (Syn) aggregates, implicated in disease pathology. A promising avenue in PD treatment involves targeting Syn aggregation. Recent findings from our research have shown that 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylethanol (DOPET) possess the ability to impede the formation of Syn fibrils by disrupting the aggregation process. Notably, these compounds primarily engage in noncovalent interactions with the protein, leading to the formation of off-pathway oligomers that deter fibril growth. Through proteolysis studies and mass spectrometry (MS) analysis, we have identified potential covalent modifications of Syn in the presence of DOPAC, although the exact site remains elusive. Employing molecular dynamics simulations, we delved into how DOPAC-induced covalent alterations might affect the mechanism of Syn aggregation. Our findings indicate that the addition of a covalent adduct on certain residues enhances fibril flexibility without compromising its secondary structure stability. Furthermore, in the monomeric state, the modified residue fosters novel bonding interactions, thereby influencing long-range interactions between the N- and C-termini of the protein. © 2024 International Union of Biochemistry and Molecular Biology.},

note = {Cited by: 1},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gregoris2024,

title = {In Silico Exploration of AHR-HIF Pathway Interplay: Implications for Therapeutic Targeting in ccRCC},

author = { Francesco Gregoris and Giovanni Minervini and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85205114282\&doi=10.3390%2fgenes15091167\&partnerID=40\&md5=4358b236c257d898f6c44e2639ebbd9d},

doi = {10.3390/genes15091167},

issn = {20734425},

year  = {2024},

date = {2024-01-01},

abstract = {The oxygen-sensing pathway is a crucial regulatory circuit that defines cellular conditions and is extensively exploited in cancer development. Pathogenic mutations in the von Hippel\textendashLindau (VHL) tumour suppressor impair its role as a master regulator of hypoxia-inducible factors (HIFs), leading to constitutive HIF activation and uncontrolled angiogenesis, increasing the risk of developing clear cell renal cell carcinoma (ccRCC). HIF hyperactivation can sequester HIF-1β, preventing the aryl hydrocarbon receptor (AHR) from correctly activating gene expression in response to endogenous and exogenous ligands such as TCDD (dioxins). In this study, we used protein\textendashprotein interaction networks and gene expression profiling to characterize the impact of VHL loss on AHR activity. Our findings reveal specific expression patterns of AHR interactors following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and in ccRCC. We identified several AHR interactors significantly associated with poor survival rates in ccRCC patients. Notably, the upregulation of the androgen receptor (AR) and retinoblastoma-associated protein (RB1) by TCDD, coupled with their respective downregulation in ccRCC and association with poor survival rates, suggests novel therapeutic targets. The strategic activation of the AHR via selective AHR modulators (SAhRMs) could stimulate its anticancer activity, specifically targeting RB1 and AR to reduce cell cycle progression and metastasis formation in ccRCC. Our study provides comprehensive insights into the complex interplay between the AHR and HIF pathways in ccRCC pathogenesis, offering novel strategies for targeted therapeutic interventions. © 2024 by the authors.},

note = {Cited by: 0; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bellanda2024,

title = {A PDZ scaffolding/CaM-mediated pathway in Cryptochrome signaling},

author = { Massimo Bellanda and Milena Damulewicz and Barbara Zambelli and Elisa Costanzi and Francesco Gregoris and Stefano Mammi and Silvio C. E. Tosatto and Rodolfo Costa and Giovanni Minervini and Gabriella M. Mazzotta},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85185346556\&doi=10.1002%2fpro.4914\&partnerID=40\&md5=9d3ca7169c5c85e7e43289adbe2c3e24},

doi = {10.1002/pro.4914},

issn = {09618368},

year  = {2024},

date = {2024-01-01},

abstract = {Cryptochromes are cardinal constituents of the circadian clock, which orchestrates daily physiological rhythms in living organisms. A growing body of evidence points to their participation in pathways that have not traditionally been associated with circadian clock regulation, implying that cryptochromes may be subject to modulation by multiple signaling mechanisms. In this study, we demonstrate that human CRY2 (hCRY2) forms a complex with the large, modular scaffolding protein known as Multi-PDZ Domain Protein 1 (MUPP1). This interaction is facilitated by the calcium-binding protein Calmodulin (CaM) in a calcium-dependent manner. Our findings suggest a novel cooperative mechanism for the regulation of mammalian cryptochromes, mediated by calcium ions (Ca2+) and CaM. We propose that this Ca2+/CaM-mediated signaling pathway may be an evolutionarily conserved mechanism that has been maintained from Drosophila to mammals, most likely in relation to its potential role in the broader context of cryptochrome function and regulation. Further, the understanding of cryptochrome interactions with other proteins and signaling pathways could lead to a better definition of its role within the intricate network of molecular interactions that govern circadian rhythms. © 2024 The Protein Society.},

note = {Cited by: 0},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rocca20231181,

title = {Mutational Screening of Androgen Receptor Gene in 8224 Men of Infertile Couples},

author = { Maria Santa Rocca and Giovanni Minervini and Cinzia Vinanzi and Alberto Bottacin and Federica Lia and Carlo Foresta and Maria Pennuto and Alberto Ferlin},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152486041\&doi=10.1210%2fclinem%2fdgac671\&partnerID=40\&md5=b7a9f7deadbf767f38e0f33108febd94},

doi = {10.1210/clinem/dgac671},

issn = {0021972X},

year  = {2023},

date = {2023-01-01},

abstract = {Context: Mutations in the androgen receptor (AR) gene might be associated with infertility mainly because they cause various degrees of androgen insensitivity. Objective: The aim of the study was to evaluate the frequency and type of AR variants in a large cohort of infertile males. Methods: A total of 8224 males of Italian idiopathic infertile couples were referred to the University Hospital of Padova. The main outcome measures were mutational screening of AR, computational, and functional analyses. Results: We found 131 patients (1.6%) harboring 45 variants in AR gene, of which 18 were novel missense AR variants. Patients with AR gene variants had lower sperm count (P = .048), higher testosterone (T) concentration (P \< .0001), and higher androgen sensitivity index (ASI) (luteinizing hormone × T, P \< .001) than patients without variants. Statistical analyses found T ≥ 15.38 nmol/L and ASI ≥ 180 IU × nmol/L2 as the threshold values to discriminate with good accuracy patients with AR variants. Patients with oligozoospermia and T ≥ 15.38 nmol/L had a 9-fold increased risk of harboring mutations compared with patients with normal sperm count and T \< 15.38 nmol/L (odds ratio 9.29, 95% CI 5.07-17.02). Using computational and functional approaches, we identified 2 novel variants, L595P and L791I, as potentially pathogenic. Conclusion: This is the largest study screening AR gene variants in men of idiopathic infertile couples. We found that the prevalence of variants increased to 3.4% in oligozoospermic subjects with T ≥ 15.38 nmol/L. Conversely, more than 80% of men with AR gene variants had low sperm count and high T levels. Based on our findings, we suggest AR sequencing as a routine genetic test in cases of idiopathic oligozoospermia with T ≥ 15.38 nmol/L. © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.},

note = {Cited by: 2; All Open Access, Bronze Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}