Luca De Gioia

Luca De Gioia
Università degli Studi di Milano-Bicocca | UNIMIB · Department of Biotechnology and Biosciences

About

292
Publications
21,300
Reads
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9,342
Citations
Citations since 2016
71 Research Items
3342 Citations
20162017201820192020202120220100200300400500600
20162017201820192020202120220100200300400500600
20162017201820192020202120220100200300400500600
20162017201820192020202120220100200300400500600
Additional affiliations
January 2005 - December 2011
January 2002 - present
Università degli Studi di Milano-Bicocca
January 1996 - December 1999
University of Milan
Education
November 1984 - January 1990
University of Milan
Field of study
  • chemistry

Publications

Publications (292)
Article
De novo metalloprotein design is a remarkable approach to shape protein scaffolds toward specific functions. Here, we report the design and characterization of Due Rame 1 (DR1), a de novo designed protein housing a di‐copper site and mimicking the Type 3 (T3) copper‐containing polyphenol oxidases (PPOs). To achieve this goal, we hierarchically desi...
Article
Full-text available
Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is the familial form of a focal epilepsy characterized by hyperkinetic focal seizures, mainly arising during non-rapid eye movements (NREM) sleep. Mutations associated with ADSHE account for a small proportion of the genetically determined cases, suggesting the existence of other disease-...
Article
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Determining the redox potentials of protein cofactors and how they are influenced by their molecular neighborhoods is essential for basic research and many biotechnological applications, from biosensors and biocatalysis to bioremediation and bioelectronics. The laborious determination of redox potential with current experimental technologies pushes...
Article
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Four endemic coronaviruses infect humans and cause mild symptoms. Because previous analyses were based on a limited number of sequences and did not control for effects that affect molecular dating, we re-assessed the timing of endemic coronavirus emergence. After controlling for recombination, selective pressure, and molecular clock model, we obtai...
Article
Oxidative stress and copper dyshomeostasis are well established factors in the course of Alzheimer's disease (AD). Indeed, the pathological interaction of copper with the amyloid peptide is able to induce radical oxygen species (ROS) production through a three‐step cycle in which O 2 is gradually reduced to superoxide, oxygen peroxide and finally t...
Article
Full-text available
Coronaviruses (CoVs) have complex genomes that encode a fixed array of structural and nonstructural components, as well as a variety of accessory proteins that differ even among closely related viruses. Accessory proteins often play a role in the suppression of immune responses and may represent virulence factors. Despite their relevance for CoV ph...
Article
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Ion pairing in water solutions alters both the water hydrogen-bond network and ion solvation, modifying the dynamics and properties of electrolyte water solutions. Here, we report an anomalous intrinsic fluorescence of KCl aqueous solution at room temperature and show that its intensity increases with the salt concentration. From the ab initio dens...
Article
The electron rich Fe 2 (pdt)(RNC) 6 1 (pdt = CH 2 (CH 2 S – ) 2 ) has been used as starting point for a DFT multi‐functional study to assess the feasibility of designing a stable inverted (or rotated) disposition of the two FeL 3 pyramidal moieties in the dimetallic core, a key feature of [FeFe]‐hydrogenase cofactor. The choice of 1 was motivated b...
Article
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This work originated from the need to functionalize surfactant-coated inorganic nanoparticles for biomedical applications, a process that is limited by excess unbound surfactant. These limitations are connected to the bioconjugation of targeting molecules that are often in equilibrium between the free aliquot in solution and that which binds the su...
Article
A few bio-inorganic systems have been studied by means of modern quantum chemistry (QM) methods, such as the Density Functional Theory (DFT) in connection with a large set of basis functions. At this level, DFT has proven to give reliable (semi-quantitative) description of several properties of transition metals complexes which are either relevant...
Article
Hydrogenases are enzymes that catalyze the oxidation and production of molecular hydrogen. For about fifteen years, there have been many reports about the successful connection of these enzymes to photosensitizers with the aim of designing H2 photoproduction systems, but relatively little attention has been paid to whether and why illumination may...
Article
Full-text available
Four coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E) are endemic in human populations. All these viruses are seasonal and generate short-term immunity. Like the highly pathogenic coronaviruses, the endemic coronaviruses have zoonotic origins. Thus, understanding the evolutionary dynamics of these human viruses might provide insight i...
Article
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Ras oncoproteins play a crucial role in the onset, maintenance, and progression of the most common and deadly human cancers. Despite extensive research efforts, only a few mutant-specific Ras inhibitors have been reported. We show that cmp4-previously identified as a water-soluble Ras inhibitor-targets multiple steps in the activation and downstrea...
Article
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FeIFeI Fe2(S2C3H6)(CO)6(µ-CO) (1a–CO) and its FeIFeII cationic species (2a+–CO) are the simplest model of the CO-inhibited [FeFe] hydrogenase active site, which is known to undergo CO photolysis within a temperature-dependent process whose products and mechanism are still a matter of debate. Using density functional theory (DFT) and time-dependent...
Preprint
FeIFeI Fe2(S2C3H6)(CO)6(µ-CO) (1a-CO) and its FeIFeII cationic species (2a+-CO) are the simplest model of the CO-inhibited [FeFe] hydrogenase active site, which is known to undergo CO photolysis within a temperature- dependent process whose products and mechanism are still a matter of debate. Using Density Functional Theory (DFT) and Time-Dependent...
Article
Full-text available
In view of the depletion of fossil fuel reserves and climatic effects of greenhouse gas emissions, Ni,Fe-containing carbon monoxide dehydrogenase (Ni-CODH) enzymes have attracted increasing interest in recent years for their capability to selectively catalyze the reversible reduction of CO2 to CO (CO2 + 2H+ + 2e- ⇌ CO + H2O). The possibility of con...
Preprint
Full-text available
Understanding the evolutionary dynamics of the four human endemic coronaviruses might provide insight into the future trajectories of SARS-CoV-2 evolution. We re-assessed the timing of endemic coronavirus emergence and we show that all viruses entered human populations in a time-frame ranging from ~500 to 55 years ago. Because the three highly path...
Article
Oxidative stress and metal dyshomeostasis are considered as crucial factors in the pathogenesis of Alzheimer's disease (AD). Indeed, transition metal ions such as Cu(II) can generate Reactive Oxygen Species (ROS) via O2 Fenton-like reduction, catalyzed by Cu(II) coordinated to the Amyloid beta (Aβ) peptide. Despite intensive effort, the mechanisms...
Article
It was recently discovered that some redox proteins can thermodynamically and spatially split two incoming electrons towards different pathways, resulting in the one‐electron reduction of two different substrates, featuring reduction potential respectively higher and lower than the parent reductant. This energy conversion process, referred to as el...
Article
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This perspective aims at illustrating a computational viewpoint on some specific issues concerning structure-activity relationships related to [FeFe]-hydrogenase ([FeFe]-H2ase) biomimicry. Most of research outlined herein have been addressed by means of Density Functional Theory (DFT) based tools, in some cases in conjunction with experimental tech...
Article
The electrochemical reduction of complexes [Fe2(CO)4(k2‐phen)(μ‐xdt)] (phen = 1,10‐phenanthroline ; xdt = pdt (1), adtiPr (2)) in MeCN‐[Bu4N][PF6] 0.2 M is described as a two‐reduction process. DFT calculations show that 1 and its reduced form 1‐ display metal‐ and phenanthroline‐centered frontier orbitals (LUMO and SOMO) indicating the non‐innocen...
Article
A large number of catalysts for hydrogen evolution reaction (HER) that are related (structurally and/or functionally) to the active site of [FeFe]-hydrogenases (H-cluster) has been proposed in the past few decades. Very recently, a novel recipe for HER catalysts has been added to the list. This consists in the combination of a diiron core, a ligand...
Article
The unique properties of liquid water mainly arise from its hydrogen bond network. The geometry and dynamics of this network play a key role in shaping the characteristics of soft matter, from simple solutions to biosystems. Here we report an anomalous intrinsic fluorescence of HCl and NaOH aqueous solutions at room temperature, that shows importan...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Article
The potentials of redox systems involving nitrogen, oxygen and metal ions of the first row transition series have been computed according to the general approach of the grand canonical ensemble which leads to the equilibrium value of the reduction potential via a (complete) sampling of configuration space at a given temperature. The approach is a s...
Article
The apparently simple dihydrogen formation from protons and electrons (2H⁺ + 2e⁻H2) is one of the most challenging reactions in nature. It is catalyzed by metalloenzymes of amazing complexity, called hydrogenases. A better understanding of the chemistry of these enzymes, especially that of the [NiFe]-hydrogenases subgroup, has important implication...
Article
A DFT study on the H2 catalytic oxidation in both the [FeFe]‐H2ase active site and biomimicry reveals that the origin of the higher performance of nature is due to an enzyme core endowed with both electron‐richness (supporting electron removal) and a single electron‐poor Fe (supporting H2 binding). The key ligand ensuring both features is CN⁻ becau...
Article
The electrochemical behavior of complexes [FeMo(CO)5(κ²-dppe)(μ-pdt)] (1) and [FeMo(CO)4(MeCN)( κ²-dppe)(μ-pdt)] (2), in the absence and in the presence of acid, has been investigated. The reduction of 1 follows at slow scan rates, in CH2Cl2-[NBu4][PF6] and acid-free media, an ECrevE mechanism that is supported by cyclic voltammetry (CV) experiment...
Article
Full-text available
Catalytic H2 oxidation has been dissected by DFT in the key steps common both to the Fe2 unit of the [FeFe]‐hydrogenase cofactor and to selected biomimicry. The aim was to elucidate molecular details underlying the very different performances of the two systems. We found out that the higher enzyme performance is based on a single Fe atom that is ma...
Article
Alzheimer’s disease (AD) involves a number of factors including an anomalous interaction of copper with the amyloid peptide (Aβ), inducing oxidative stress with radical oxygen species (ROS) production through a three-step Fenton-like cycle in which O2 is gradually reduced to superoxide, oxygen peroxide and finally to OH radicals. The purpose of thi...
Article
Electrochemical oxidation of the complex [Fe2(CO)4(κ2‐dmpe)(µ‐adtBn)] (adtBn = (SCH2)2NCH2C6H5, dmpe = Me2PCH2CH2PMe2) (1) has been studied by cyclic voltammetry (CV) in acetonitrile and in dichloromethane in presence of various substrates L (L =MeCN, trimethylphosphite, isocyanide). The oxidized species, [1‐MeCN](PF6)2, [1‐(P(OMe)3)2](PF6)2 and [1...
Conference Paper
Full-text available
Introduction Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumour progression. Recent studies reported an association between the tumorigenic potential, metastasis and chemoresistance of several type of breast cancer cells...
Article
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Hepatitis C virus (HCV) belongs to the Hepacivirus genus and is genetically heterogeneous, with seven major genotypes further divided into several recognized subtypes. HCV origin was previously dated in a range between ∼200 and 1000 years ago. Hepaciviruses have been identified in several domestic and wild mammals, the largest viral diversity being...
Article
FeFe hydrogenases catalyse H2 oxidation and production using a "H-cluster", where two Fe ions are bound by an aza-dithiolate (adt) ligand. Various hypotheses have been proposed (by us and others) to explain that the enzyme reversibly inactivates under oxidizing, anaerobic conditions: intramolecular binding of the N atom of adt, formation of the so-...
Article
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A library of GlcNAc-6 or 1P analogues was designed and each compound was computationally evaluated through docking studies for its binding affinity to AGM1/PGM3. The compounds with the highest binding affinity ranked through a docking score, were synthesized and screened for their ability to inhibit the production of UDP-GlcNAc. A glycofused oxazol...
Article
Full-text available
Cancer aberrant N- and O-linked protein glycosylation, frequently resulting from an augmented flux through the Hexosamine Biosynthetic Pathway (HBP), play different roles in tumor progression. However, the low specificity and toxicity of the existing HBP inhibitors prevented their use for cancer treatment. Here we report the preclinical evaluation...
Article
The biological reduction of dinitrogen (N2) to ammonia is catalyzed by the complex metalloenzyme nitrogenase. Structures of the nitrogenase component proteins, Iron (Fe) protein and Molybdenum‑iron (MoFe) protein, and the stabilized complexes these component proteins, have been determined, providing a foundation for a number of fundamental aspects...
Article
The extraordinary capability of [NiFe]-hydrogenases to catalyse the reversible interconversion of protons and electrons into dihydrogen (H2) has stimulated numerous experimental and theoretical studies addressed to the direct utilization of these enzymes in H2 production processes. Unfortunately, the introduction of these natural H2-catalysts into...
Article
The photochemistry of the [FeFe] hydrogenases model [Fe2(edt)(CO)4(PMe3)2] (edt = 1-2 ethane-dithiolate, (1) is investigated at Time-Dependent Density Functional Theory (TDDFT) level, focusing on the effect of the phosphine ligands on the early stages of the photodynamic of the system compared to that of the all CO model Fe2(pdt)(CO)6 (2) (pdt = 1-...
Article
DFT has been used to investigate viable mechanisms of the hydrogen evolution reaction (HER) electrocatalyzed by [Fe2(CN){μ-CN(Me)2}(μ-CO)(CO)(Cp)2] (1) in AcOH. Molecular details underlying the proposed ECEC electrochemical sequence have been studied, and the key functionalities of CN(-) and amino-carbyne ligands have been elucidated. After the fir...
Article
Transferrin (Tf) is the major iron-transporting protein in the human body and, for this reason, has been extensively studied in biomedicine. This protein undergoes a complex glycosylation process leading to several glycoforms, some of which are important in the diagnosis of alcohol abuse and of congenital glycosylation defects under the collective...
Article
In the enzyme FeFe hydrogenase, hydrogen oxidation and production occur at the H-cluster, a Fe6S6 active site that bears intrinsic carbonyl and cyanide ligands. This enzyme has been coupled to photosensitizers to design H2 photoproduction systems, and yet, according to earlier reports, the enzyme from Desulfovibrio desulfuricans is "easily destroye...
Article
The protein ataxin-3 (ATX3) triggers an amyloid-related neurodegenerative disease when its polyglutamine stretch is expanded beyond a critical threshold. We formerly demonstrated that the polyphenol epigallocatechin-3-gallate (EGCG) could redirect amyloid aggregation of a full-length, expanded ATX3 (ATX3-Q55) towards non-toxic, soluble, SDS-resista...
Article
The angiogenin protein (Ang) is a member of the vertebrate-specific secreted ribonucleases and one of the most potent angiogenic factors known. Ang is a normal constituent of human plasma and its concentration increases in some physiological and pathological conditions to promote neovascularization. Ang was originally identified as an angiogenic tu...
Article
Electrochemical studies of [Fe2(CO)4(2-dmpe)(µ-dithiolate)] (dithiolate = adtBn, pdt) and density functional theory (DFT) calculations reveal the striking influence of an amine functionality in the dithiolate bridge on their oxidative properties. [Fe2(CO)4(2-dmpe)(µ-adtBn)] (1) undergoes two one-electron oxidation steps, the first being partially...
Article
The Mo/Cu-dependent CO dehydrogenase from Oligotropha carboxidovorans is an enzyme that is able to catalyze CO oxidation to CO2; moreover, it can also oxidize H2, thus eliciting a characteristic EPR signal. Interestingly, the Ag-substituted enzyme form proved unable to catalyze H2 oxidation. In the present contribution, we characterized the reactiv...
Article
It is successfully shown that photocatalytic proton reduction to dihydrogen in the presence of a sacrificial electron donor, such as trimethylamine (TEA) and ascorbate, can be driven by compact sensitizer–catalyst dyads, that is, dithiolate-bridged [FeFe] hydrogenase models tethered to organic sensitizers, such as fluorenes and silafluorenes (1 a–4...
Article
[NiFe]-hydrogenases catalyse the relevant H2 → 2H⁺ + 2e⁻ reaction. Aerobic oxidation or anaerobic oxidation of this enzyme yields two inactive states called Ni-A and Ni-B. These states differ for the reactivation kinetics which are slower for Ni-A than Ni-B. While there is a general consensus on the structure of Ni-B, the nature of Ni-A is still co...
Article
FeFe hydrogenases catalyze H2 oxidation and formation at an inorganic active site (the "H-cluster"), which consists of a [Fe2(CO)3(CN)2(dithiomethylamine)] subcluster covalently attached to a Fe4S4 subcluster. This active site is photosensitive: visible light has been shown to induce the release of exogenous CO (a reversible inhibitor of the enzyme...
Article
Full-text available
Binding-induced conformational changes of a protein at regions distant from the binding site may play crucial roles in protein function and regulation. The p53 tumour suppressor is an example of such an allosterically regulated protein. Little is known, however, about how DNA binding can affect distal sites for transcription factors. Furthermore, t...
Article
Filovirus infection is mediated by engagement of the surface-exposed glycoprotein (GP) by its cellular receptor, NPC1 (Niemann-Pick C1). Two loops in the C domain of NPC1 (NPC1-C) bind filovirus GP. Herein we show that filovirus GP and NPC1-C evolve under mutual selective pressure. Analysis of a large mammalian phylogeny indicated that strong funct...
Article
Aim of this contribution is to review some recent quantum mechanical approaches used to compute the redox potentials of transition metal complexes, with the emphasis on copper and iron species, which are particularly relevant in inorganic biochemistry and in synthetic chemistry of bio-mimetic compounds. The paper presents also new DFT results obtai...
Article
Full-text available
We synthesized a small library of N-spirofused bicyclic derivatives of 1-deoxynojirimycin (DNJ), as quaternary ammonium salts, through a double SN2 annulation process. The spirofused rings are of different size and structural characteristics. Preliminary biological evaluation showed no antibacterial activity towards both Gram+ and Gram- bacteria. T...
Article
The serine-threonine protein kinase Akt, also known as protein kinase B, is a key component of the phosphoinositide 3-kinase (PI3K)-Akt-mTOR axis. Deregulated activation of this pathway is frequent in human tumors and Akt-dependent signaling appears to be critical in cell survival. PI3K activation generates 3-phosphorylated phosphatidylinositols th...
Article
The complement system is an innate immunity effector mechanism its action is antagonized by a wide array of pathogens and complement evasion determines the virulence of several infections. We investigated the evolutionary history of the complement system and of bacterial-encoded complement-interacting proteins. Complement components targeted by sev...
Article
According to different studies, the interaction between amyloid β-peptide (Aβ) and copper ions could yield radical oxygen species production, in particular the highly toxic hydroxyl radical OH(·) that is suspected to contribute to Alzheimer's disease pathogenesis. Despite intensive experimental and computational studies, the nature of the interacti...
Data
2 O model (QTAIM analysis, MO diagrams); ii) details of the computational method adopted iii) pictures of the van der Waals adducts, of the His 2 -H 2 O model and of the His 2 -NH 2 PES scan; iv) the atomic coordinates of all S = 0 η1 adduct and η2 S = 0 products
Article
Full-text available
Middle East respiratory syndrome coronavirus (MERS-CoV) originated in bats and spread to humans via zoonotic transmission from camels. We analyzed the evolution of the spike (S) gene in betacoronaviruses (betaCoVs) isolated from different mammals, in bat coronavirus populations, as well as in MERS-CoV strains from the current outbreak. Results indi...
Article
Density functional theory has been used to study diiron dithiolates [HFe2(xdt)(PR3)n(CO)5-nX] (n = 0, 2, 4; R = H, Me, Et; X = CH3S(-), PMe3, NHC = 1,3-dimethylimidazol-2-ylidene; xdt = adt, pdt; adt = azadithiolate; pdt = propanedithiolate). These species are related to the [FeFe]-hydrogenases catalyzing the 2H(+) + 2e(-) ↔ H2 reaction. Our study...
Article
To learn from Nature how to create an efficient hydrogen-producing catalyst, much attention has been paid to the investigation of structural and functional biomimics of the active site of [FeFe]-hydrogenase. To understand their catalytic activities, the μ-S atoms of the dithiolate bridge have been considered as possible basic sites during the catal...
Article
The reduction of the Fe(II)Fe(II) complex [Fe2(CO)2{P(OMe)3}2(κ2-IMe-CH2-IMe)(μ-CO)(μ-pdt)]2+ (2P2+; pdt = S(CH2)3S), which is a synthetic model of the H cluster of the [FeFe] hydrogenases in its inactive state, has been investigated electrochemically and theoretically (by density functional theory, DFT) in order to determine the mechanisms, interm...
Article
Full-text available
The [FeFe] hydrogenase is a highly sophisticated enzyme for the synthesis of hydrogen via a biological route. The rotated state of the H-cluster in the [Fe(I)Fe(I)] form was found to be an indispensable criteria for an effective catalysis. Mimicking the specific rotated geometry of the [FeFe] hydrogenase active site is highly challenging as no prot...
Article
[FeFe]-hydrogenases are the most efficient biological catalysts available for the H2 evolution reaction. Their active site – the H-cluster – features a diiron subsite which has the peculiar characteristic of bearing cyanide groups hydrogen-bonded to the apoprotein as well as carbonyl ligands. Notably, one of the CO ligands is disposed in bridging p...