Massimo Coletta

Massimo Coletta
University of Rome Tor Vergata | UNIROMA2 · Dipartimento di Scienze Cliniche e Medicina Traslazionale

Degree in Medicine and Surgery

About

332
Publications
23,417
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11,313
Citations
Citations since 2016
58 Research Items
2886 Citations
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
20162017201820192020202120220100200300400500
Introduction
Skills and Expertise

Publications

Publications (332)
Article
Full-text available
Nitrobindins (Nbs) are all-β-barrel heme proteins and are present in prokaryotes and eukaryotes. Although their function(s) is still obscure, Nbs trap NO and inactivate peroxynitrite. Here, the kinetics of peroxynitrite scavenging by ferric Danio rerio Nb (Dr-Nb(III)) in the absence and presence of CO2 is reported. The Dr-Nb(III)-catalyzed scavengi...
Article
Nitrobindins (Nbs) are all-β-barrel heme-proteins present in all the living kingdoms. Nbs inactivate reactive nitrogen species by sequestering NO, converting NO to HNO2, and isomerizing peroxynitrite to NO3⁻ and NO2⁻. Here, the spectroscopic characterization of ferric Danio rerio Nb (Dr-Nb(III)) and NO scavenging through the reductive nitrosylation...
Article
Nitrobindins (Nbs) are all-β-barrel heme-proteins present in prokaryotes and eukaryotes. Although the physiological role(s) of Nbs are still unclear, it has been postulated that they are involved in the NO/O2 metabolism, which is particularly relevant in fishes for the oxygen supply. Here, the reactivity of ferrous Danio rerio Nb (Dr-Nb(II)) toward...
Article
Full-text available
Cationic porphyrins exhibit an amazing variety of binding modes and inhibition mechanisms of 20S proteasome. Depending on the spatial distribution of their electrostatic charges, they can occupy different sites on α rings of 20S proteasome by exploiting the structural code responsible for the interaction with regulatory proteins. Indeed, they can a...
Article
Hemoglobin and myoglobin are generally taken as molecular models of all-α-helical heme-proteins. On the other hand, nitrophorins and nitrobindins (Nb), which are arranged in 8 and 10 β-strands, respectively, represent the molecular models of all-β-barrel heme-proteins. Here, kinetics of the hydroxylamine- (HA-) mediated oxidation of ferrous Mycobac...
Article
Full-text available
Carfilzomib is a last generation proteasome inhibitor (PI) with proven clinical efficacy in the treatment of relapsed/refractory multiple myeloma. This drug is considered to be extremely specific in inhibiting the chymotrypsin-like activity of the 20S proteasome, encoded by the β5 subunit, overcoming some bortezomib limitations, the first PI approv...
Article
Full-text available
Neuroglobin (Ngb), the third member of the globin family, was discovered in human and murine brains in 2000. This monomeric globin is structurally similar to myoglobin (Mb) and hemoglobin (Hb) α and β subunits, but it hosts a bis-histidyl six-coordinated heme-Fe atom. Therefore, the heme-based reactivity of Ngb is modulated by the dissociation of t...
Article
Full-text available
Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27)...
Article
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The complex multidimensional skeletal organization can adapt its structure in accordance with external contexts, demonstrating excellent self-renewal capacity. Thus, optimal extracellular environmental properties are critical for bone regeneration and inextricably linked to the mechanical and biological states of bone. It is interesting to note tha...
Article
The molecular mechanism of O2 binding to hemoglobin (Hb) has been critically reviewed on the basis of the information built up in the last decades. It allows to describe in detail from the kinetic and thermodynamic viewpoint the process of O2 uptake in the lungs and release to the tissues, casting some light on the physiological and pathological as...
Article
The O2-mediated oxidation of all-β-barrel ferrous nitrosylated nitrobindin from A. thaliana (At-Nb(II)-NO), Mycobaterium tuberculosis (Mt-Nb(II)-NO), and Homo sapiens (Hs-Nb(II)-NO) to ferric derivative (At-Nb(III), Mt-Nb(III), and Hs-Nb(III), respectively) has been investigated at pH 7.0 and 20.0 °C. Unlike ferrous nitrosylated horse myoglobin, hu...
Article
Full-text available
Steroid-induced glaucoma is a severe pathological condition, sustained by a rapidly progressive increase in intraocular pressure (IOP), which is diagnosed in a subset of subjects who adhere to a glucocorticoid (GC)-based therapy. Molecular and clinical studies suggest that either natural or synthetic GCs induce a severe metabolic dysregulation of T...
Preprint
Full-text available
Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with strong in vitro and in vivo anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing h...
Article
Full-text available
Cytidine 5’-diphosphocholine has been widely studied in systemic neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and brain ischemia. The rationale for the use of citicoline in ophthalmological neurodegenerative diseases, including glaucoma, anterior ischemic optic neuropathy, and diabetic retinopathy, is founded on its mu...
Article
Full-text available
Structural and functional properties of ferrous Mycobacterium tuberculosis (Mt-Nb) and human (Hs-Nb) nitrobindins (Nbs) were investigated. At pH 7.0 and 25.0 °C, the unliganded Fe(II) species is penta-coordinated and unlike most other hemoproteins no pH-dependence of its coordination was detected over the pH range between 2.2 and 7.0. Further, desp...
Article
Haptoglobin (Hp) counterbalances the adverse effects of extra-erythrocytic hemoglobin (Hb) by trapping the αβ dimers of Hb in the bloodstream. In turn, the Hp:Hb complexes display Hb-like reactivity. Here, the kinetics of NO dissociation from ferrous nitrosylated Hp:Hb complexes (i.e., Hp1–1:Hb(II)-NO and Hp2–2:Hb(II)-NO, respectively) are reported...
Article
Full-text available
Ferric nitrobindins (Nbs) selectively bind NO and catalyze the conversion of peroxynitrite to nitrate. In this study, we show that NO scavenging occurs through the reductive nitrosylation of ferric Mycobacterium tuberculosis and Homo sapiens nitrobindins (Mt-Nb(III) and Hs-Nb(III), respectively). The conversion of Mt-Nb(III) and Hs-Nb(III) to Mt-Nb...
Article
Full-text available
The present study provides new evidence that cationic porphyrins may be considered as tunable platforms to interfere with the structural “key code” present on the 20S proteasome α-rings and, by consequence, with its catalytic activity. Here, we describe the functional and conformational effects on the 20S proteasome induced by the cooperative bindi...
Article
In the Fall of 2019 a sudden and dramatic outbreak of a pulmonary disease (Coronavirus Disease COVID-19), due to a new Coronavirus strain (i.e., SARS-CoV-2), emerged in the continental Chinese area of Wuhan and quickly diffused throughout the world, causing up to now several hundreds of thousand deaths. As for common viral infections, the crucial e...
Article
Haptoglobin (Hp) belongs to the family of acute-phase plasma proteins and represents the most important plasma detoxifier of hemoglobin (Hb). The basic Hp molecule is a tetrameric protein built by two α/β dimers. Each Hp α/β dimer is encoded by a single gene and is synthesized as a single polypeptide. Following post-translational protease-dependent...
Article
Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of...
Article
Full-text available
Aims: Nitrobindins (Nbs) are evolutionary conserved all-β-barrel heme-proteins displaying a highly solvent-exposed heme-Fe(III) atom. The physiological role(s) of Nbs is almost unknown. Here, the structural and functional properties of the Mycobacterium tuberculosis Nb (Mt-Nb(III)) and Homo sapiens Nb (Hs-Nb(III)) have been investigated and compar...
Article
Citicoline or CDP-choline is a drug, made up by a cytidine 5’-diphosphate moiety and choline, which upon adsorption is rapidly hydrolyzed into cytidine 5’-diphosphate and choline, easily bypassing the blood-brain barrier. Once in the brain, these metabolites are used to re-synthesize citicoline in neurons and in the other cell histotypes which upta...
Article
Haptoglobin (Hp) counterbalances the adverse effects of extra-erythrocytic hemoglobin (Hb) trapping the αβ dimers of Hb. In turn, the Hp:Hb complexes display heme-based reactivity. Here, the kinetics of cyanide and carbon monoxide dissociation from ferrous-ligated Hp:Hb complexes are reported at pH 7.0 and 20.0 °C. Cyanide dissociation from Hp1-1:H...
Article
Haptoglobin (Hp) binds human hemoglobin (Hb), contributing to prevent extra-erythrocytic Hb-induced damage. Hp forms preferentially complexes with αβ dimers, displaying heme-based reactivity. Here, kinetics and thermodynamics of fluoride and azide binding to ferric human Hb (Hb(III)) complexed with the human Hp phenotypes 1-1 and 2-2 (Hp1-1:Hb(III)...
Article
Full-text available
Several lines of evidence point to a compromised proteostasis associated to a reduction of the Ubiquitin Proteasome System (UPS) activity in patients affected by Alzheimer’s Disease (AD) and suggest that the amyloid β peptide (Aβ) is an important player in the game. Inspired also by many reports, underlining the presence of ubiquitin (Ub) in the am...
Article
The hexa-coordinated metal center of horse heart cytc (cytc) is at the root of its low reactivity. In contrast, carboxymethylated cytc (CM-cytc) displays myoglobin-like properties. Herein, kinetics of CO binding to ferrous CM-cytc (CM-cytc(II)) and of the irreversible oxidation of ferrous carbonylated CM-cytc (CM-cytc(II)-CO) by hydroxylamine (HA),...
Article
Microperoxidase-11 (MP11) is an undecapeptide derived from horse heart cytochrome c, which is considered as a heme-protein model. Here, the reductive nitrosylation of ferric MP11 (MP11(III)) under anaerobic conditions has been investigated between pH 7.4 and 9.2, at T = 20.0 °C. At pH ≤ 7.7, NO binds reversibly to MP11(III) leading to the formation...
Article
Full-text available
The interaction of insulin-degrading enzyme (IDE) with the main intracellular proteasome assemblies (i.e, 30S, 26S and 20S) was analyzed by enzymatic activity, mass spectrometry and native gel electrophoresis. IDE was mainly detected in association with assemblies with at least one free 20S end and biochemical investigations suggest that IDE compet...
Article
A recently published paper applies cryo-electron microscopy (EM) studies and biochemical/genetic approaches for the elucidation of the mechanisms linking nucleotide binding by ATPases, proteasome conformation dynamics, and gate opening of the 20S core particle. These insights potentially represent a milestone in our understanding of the structural...
Article
Haptoglobin (Hp) binding to hemoglobin (Hb) is crucial to prevent extra-erythrocytic Hb-induced damage; in turn, Hp:Hb complexes display heme-based reactivity. Here, the nitrite reductase activity of ferrous human Hb (Hb(II)) complexed with the human Hp phenotypes 1-1 and 2-2 (Hp1-1:Hb(II) and Hp2-2:Hb(II), respectively) is reported to highlight th...
Article
Full-text available
Decreased mechanical loading on bones, such as prolonged bed rest and microgravity during space flights, leads to the development of an osteoporotic-like phenotype. Although osteoblast hypo-functionality is reported to be involved in the progression of bone pathological conditions, the cellular mechanisms of this process remain largely unknown. The...
Article
Haptoglobin (Hp) sequesters hemoglobin (Hb) preventing the Hb-based damage occurring upon its physiological release into plasma. Here, reductive nitrosylation of ferric human hemoglobin [Hb(III)] bound to human haptoglobin (Hp) 1-1 and 2-2 [Hp1-1:Hb(III) and Hp2-2:Hb(III), respectively] has been investigated between pH 7.5 and 9.5, at T=20.0 °C. Ov...
Article
Full-text available
Significant advances in the understanding of the molecular determinants of fibrillogenesis can be expected from comparative studies of the aggregation propensities of proteins with highly homologous structures but different folding pathways. Here, we fully characterize, by means of stopped-flow, T-jump, CD and DSC experiments, the unfolding mechani...
Article
Full-text available
Dystroglycan (DG) is a membrane receptor, belonging to the dystrophin-glycoprotein complex (DGC) and formed by two subunits, α-dystroglycan (α-DG) and β-dystroglycan (β -DG). The C-terminal domain of α-DG and the N-terminal extracellular domain of β -DG are connected, providing a link between the extracellular matrix and the cytosol. Under patholog...
Article
The enzyme Zmp1 is a zinc-peptidase having a critical role in M. tuberculosis pathogenicity. Here we describe the identification of a small set of Zmp1 inhibitors based on a novel 8-hydroxyquinoline-2-hydroxamate scaffold. Among the synthesized compounds, 1c was the most potent Zmp1 inhibitor known to date, and its binding mode was analysed both th...
Article
Full-text available
The importance of allosteric proteasome inhibition in the treatment of cancer is becoming increasingly evident. Motivated by this urgent therapeutic need, we have recently identified cationic porphyrins as a highly versatile class of molecules able to regulate proteasome activity by interfering with gating mechanisms. In the present study, the mapp...
Article
Human serum heme-albumin (HSA-heme-Fe) displays heme-based ligand binding and (pseudo-)enzymatic properties. Here, the effect of the prototypical drug warfarin on kinetics and thermodynamics of NO binding to ferric and ferrous HSA-heme-Fe (HSA-heme-Fe(III) and HSA-heme-Fe(II), respectively) and on the NO-mediated reductive nitrosylation of the heme...
Article
Hydroxylamine (HA) is an oxidant of ferrous globins and its action has been reported to be inhibited by CO, even though this mechanism has not been clarified. Here, kinetics of the HA-mediated oxidation of ferrous carbonylated Mycobacterium tuberculosis truncated hemoglobin N and O (Mt-trHbN(II)-CO and Mt-trHbO(II)-CO, respectively) and Campylobact...
Article
Full-text available
Insulin-degrading enzyme (IDE) is a ubiquitous zinc peptidase of the inverzincin family, which has been initially discovered as the enzyme responsible for insulin catabolism; therefore, its involvement in the onset of diabetes has been largely investigated. However, further studies on IDE unraveled its ability to degrade several other polypeptides,...
Article
Substantial evidence has accumulated over the last decade indicating that diverse age-related neurodegenerative disorders share a common pathogenic mechanism: the misfolding, aggregation and accumulation of proteins (termed “amyloid”) in neuronal tissues. The latest studies suggest that, in principle, any deficiency in protein homeostasis (proteost...
Article
Full-text available
Proteases are a class of enzymes that lower the activation energy for the cleavage of the peptide bonds by polarizing the carbonyl group. The catalytic mechanism of proteases is characterized by the formation and the dissociation of a tetrahedral acyl-intermediate. The rate-limiting step in catalysis is either the acylation process (leading to the...
Article
Full-text available
Rett syndrome (RTT) is a neurodevelopmental disorder, mainly affecting females, which is associated to a mutation on the methyl-CpG-binding protein 2 gene. In the pathogenesis and progression of classic RTT, red blood cell (RBC) morphology has been shown to be an important biosensor for redox imbalance and chronic hypoxemia. Here we have evaluated...
Article
The spectroscopic and functional properties of the single Met80Ala and double Tyr67His/Met80Ala mutants of human cyt c have been investigated in their ferric and ferrous forms, and in the presence of different ligands, in order to clarify the reciprocal effect of these two residues in regulating the access of exogenous molecules into the heme pocke...
Article
Cytochrome c undergoes structural variations upon binding of cardiolipin, one of the phospholipids constituting the mitochondrial membrane. Although several mechanisms governing cytochrome c/cardiolipin (cyt c/CL) recognition have been proposed, the interpretation of the process remains, at least in part, unknown. To better define the steps charact...
Article
Somatostatin is a cyclic peptide, released in the gastrointestinal system and in the central nervous system, where it is involved in the regulation of cognitive and sensory functions, motor activity and sleep. It is a substrate of the Insulin-Degrading Enzyme (IDE) as well as a modulator of its activity and expression. In this paper, we have invest...
Article
Microperoxidase-11 (MP11) is an undecapeptide derived from horse heart cytochrome c (cytc). MP11 is characterized by a covalently linked solvent-exposed heme group, the heme-Fe atom being axially coordinated by a histidyl residue. Here, the reactions of ferrous and ferric MP11 (MP11-Fe(II) and MP11-Fe(III), respectively) with cyanide have been inve...
Article
Full-text available
The paper proposes a system for an early warning on the prosthesis performance, in particular in terms of micro- displacements of the implant-prostheses connection, enabling actions to prevent fatal damages to the structure. The system includes a sensor for micro-displacement to be inserted in the prosthesis volume, with embedded wireless communica...
Article
Horse heart carboxymethylated cytc (CM-cytc) displays myoglobin-like properties. Here, the effect of cardiolipin (CL) liposomes on the nitrite reductase activity of ferrous CM-cytc [CM-cytc-Fe(II)], in the presence of sodium dithionite, is reported between pH 5.5 and 7.6, at 20.0 °C. Cytc-Fe(II) displays a very low value of the apparent second-orde...
Article
Full-text available
The 20S proteasome is a barrel-shaped enzymatic assembly playing a critical role in proteome maintenance. Access of proteasome substrates to the catalytic chamber is finely regulated through gating mechanisms which involve aromatic and negatively charged residues located at the N-terminal tails of α subunits. However, despite the importance of gate...
Article
Spectroscopic and functional properties of human cytochrome c and its Tyr67 residue mutants (i.e., Tyr67His and Tyr67Arg) have been investigated. In the case of the Tyr67His mutant, we have observed only a very limited structural alteration of the heme pocket and of the Ω-loop involving, among others, the residue Met80 and its bond with the heme ir...
Article
Mini-myoglobin (mini-HHMb) is a fragment of horse-heart myoglobin (HHMb) considered to be the prototype of the product encoded by the central exon of the HHMb gene. For this reason, mini-HHMb has been studied extensively showing that carbonylation and oxygenation properties of the ferrous form are similar to those of the full-length protein, while...
Conference Paper
The paper proposes a system for an early warning on the prosthesis performance, in particular in terms of micro-displacements of the implant-prostheses connection, enabling actions to prevent fatal damages to the structure. The system includes a sensor for micro-displacement to be inserted in the prosthesis volume, with embedded wireless communicat...
Conference Paper
This paper aims to clarify the interdisciplinary aspects of the science of complexity in relation to complex systems. Several definitions of complexity related to different areas of engineering and mathematics are discussed. Taking an interdisciplinary approach would help in identifying commonalities between disciplines and discover new phenomena a...
Article
Full-text available
Insulin-Degrading-Enzyme (IDE) is a Zn2+-dependent peptidase highly conserved throughout evolution and ubiquitously distributed in mammalian tissues wherein it displays a prevalent cytosolic localization. We have recently demonstrated a novel Heat Shock Protein-like behaviour of IDE and its association with the 26S proteasome. In the present study,...
Article
Microperoxidase-11 (MP11) is an undecapeptide derived from horse heart cytochrome c (cyt c) and characterized by a covalently-linked solvent-exposed heme group. Here, kinetics of the NO2(-)-mediated nitrosylation of ferrous MP11 (MP11-Fe(II)) is reported. Data were obtained between pH6.4 and 8.2, at 20.0°C. The NO2(-)-mediated conversion of MP11-Fe...
Article
Full-text available
Studies of CO ligand binding revealed that two protein states with different ligand affinities exist in the protoglobin from Methanosarcina acetivorans (in MaPgb*, residue Cys(E20)101 was mutated to Ser). The switch between the two states occurs upon the ligation of MaPgb*. In this work, site-directed mutagenesis was used to explore the role of sel...
Article
Full-text available
The single-cell green alga Chlamydomonas reinhardtii harbors twelve truncated hemoglobins (Cr-TrHbs). Cr-TrHb1-1 and Cr-TrHb1-8 have been postulated to be parts of the nitrogen assimilation pathway, and of a NO-dependent signaling pathway, respectively. Here, spectroscopic and reactivity properties of Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4, all bel...
Article
Cytochrome c (cytc) is a small heme-protein located in the space between the inner and the outer membrane of the mitochondrion that transfers electrons from cytc-reductase to cytc-oxidase. The hexa-coordinated heme-Fe atom of cytc displays a very low reactivity toward ligands and does not exhibit significant catalytic properties. However, upon card...
Article
Full-text available
The hydrolysis of 4-nitrophenyl esters of hexanoate (NphOHe) and decanoate (NphODe) by human serum albumin (HSA) at Tyr411, located at the FA3-FA4 site, has been investigated between pH 5.8 and 9.5, at 22.0°C. Values of Ks, k+2, and k+2/Ks obtained at [HSA] ≥ 5×[NphOXx] and [NphOXx] ≥ 5×[HSA] (Xx is NphOHe or NphODe) match very well each other; mor...
Article
Human serum albumin (HSA) represents an important determinant of plasma oncotic pressure and a relevant factor that modulates fluid distribution between the body compartments. Moreover, HSA (i) represents the depot and transporter of several compounds, both endogenous and exogenous, (ii) affects the pharmacokinetics of many drugs, (iii) regulates c...