A5088982052- Hemoglobin structure and function
- Protein Structure and Dynamics
- Erythrocyte Function and Pathophysiology
- Neonatal Health and Biochemistry
- Photosynthetic Processes and Mechanisms
- Heme Oxygenase-1 and Carbon Monoxide
- Photoreceptor and optogenetics research
- Enzyme Structure and Function
- Pharmacogenetics and Drug Metabolism
- Microbial Natural Products and Biosynthesis
- Steroid Chemistry and Biochemistry
- Biochemical effects in animals
- Computational Drug Discovery Methods
- Porphyrin Metabolism and Disorders
- Spectroscopy and Quantum Chemical Studies
- Mass Spectrometry Techniques and Applications
- Metal-Catalyzed Oxygenation Mechanisms
- Quantum, superfluid, helium dynamics
- Advanced NMR Techniques and Applications
- Electron Spin Resonance Studies
- Advanced Fluorescence Microscopy Techniques
- RNA and protein synthesis mechanisms
- Lipid Membrane Structure and Behavior
- Hemoglobinopathies and Related Disorders
- Biochemical and Molecular Research
Sapienza University of Rome
2014-2024
Institute of Molecular Biology and Pathology
2007-2024
National Research Council
2016-2024
Istituto Pasteur
2009-2021
American Academy in Rome
2017
GF Biochemicals (Italy)
2015
Università Cattolica del Sacro Cuore
2010
European Molecular Biology Laboratory
2010
Universität Ulm
2004-2006
University of Illinois Urbana-Champaign
2004-2006
Neuroglobin (Ngb) is a globin expressed in the nervous system of humans and other organisms that involved protection brain from ischemic damage. Despite considerable interest, however, vivo function Ngb still conundrum. In this paper we report number kinetic experiments with O 2 NO have interpreted on basis 3D structure Ngb, now available for human murine metNgb NgbCO. The reaction reduced deoxyNgb slow ( t 1/2 ≈ s) ligand concentration-independent, because exogenous binding can only occur...
Although conformational changes are essential for the function of proteins, little is known about their structural dynamics at atomic level resolution. Myoglobin (Mb) paradigm to investigate because it a simple globular heme protein displaying photosensitivity iron–ligand bond. Upon laser photodissociation carboxymyoglobin Mb nonequilibrium population structures generated that relaxes over broad time range extending from picoseconds milliseconds. This process associated with migration ligand...
Abstract Neuroglobin, a recently discovered globin predominantly expressed in neuronal tissue of vertebrates, binds small, gaseous ligands at the sixth coordination position heme iron. In absence an exogenous ligand, distal histidine (His64) to iron ferrous and ferric states. The crystal structure murine (met) neuroglobin 1.5 Å reveals interesting features relevant ligand binding mechanism. Only weak selectivity is observed for two possible orientations, occupancy ratio being 70:30. Two...
Neuroglobin (Ngb), a globular heme protein expressed in the brain of vertebrates, binds oxygen reversibly, with an affinity comparable to myoglobin (Mb). Despite low sequence identity, overall 3D fold Ngb and Mb is very similar. Unlike Mb, sixth coordination position iron occupied by distal histidine, absence exogenous ligand. Endogenous ligation has been proposed as unique mechanism for regulation ligand discrimination proteins. This peculiarity might be related still-unknown physiological...
Abstract Human transferrin receptor 1 (CD71) guarantees iron supply by endocytosis upon binding of iron-loaded and ferritin. Arenaviruses the malaria parasite exploit CD71 for cell invasion epitopes on interaction with pathogenic hosts were identified. Here, we provide molecular basis ectodomain-human ferritin determining 3.9 Å resolution single-particle cryo-electron microscopy structure their complex validating our structural findings in a cellular context. The contact surfaces between...
We determined the structure of photolytic intermediate a sperm whale myoglobin (Mb) mutant called Mb-YQR [Leu-(B10)→Tyr; His(E7)→Gln; Thr(E10)→Arg] to 1.4-Å resolution by ultra-low temperature (20 K) x-ray diffraction. Starting with CO complex, illumination leads photolysis Fe–CO bond, and migration photolyzed carbon monoxide (CO*) niche in protein 8.1 Å from heme iron; this cavity corresponds that hosting an atom Xe when crystal is equilibrated xenon gas at 7 atmospheres [Tilton, R. F.,...
Work carried out over the last 30 years unveiled role of structural dynamics in controlling protein function. Cavity networks modulate trajectories and are functionally relevant; globins they have been assigned a ligand migration docking. These findings raised renewed interest for time-resolved investigations myoglobin (Mb), simple heme displaying photosensitive iron-ligand bond. Photodissociation MbCO generates nonequilibrium population structures relaxing time range extending from...
A quadruple mutant of sperm whale myoglobin was constructed to mimic the structure found in <i>Ascaris suum</i>hemoglobin. The replacements include His(E7) → Gln, Leu(B10) Tyr, Thr(E10) Arg, and Ile(G8) Phe. Single, double, triple mutants were characterized dissect out effects individual substitutions. crystal structures deoxy oxy forms determined compared with that native<i>Ascaris</i> hemoglobin. Tyr(B10) displays low O<sub>2</sub> affinity, high dissociation rate constants, heterogeneous...
Glycine oxidase from Bacillus subtilis is a homotetrameric flavoprotein of great potential biotechnological use because it catalyzes the oxidative deamination various amines and d-isomer amino acids to yield corresponding alpha-keto acids, ammonia/amine, hydrogen peroxide. Glyphosate (N-phosphonomethylglycine), broad spectrum herbicide, an interesting synthetic acid: this compound inhibits 5-enolpyruvylshikimate-3-phosphate synthase in shikimate pathway, which essential for biosynthesis...
Cytochrome P450s are heme-containing proteins that catalyze the oxidative metabolism of many physiological endogenous compounds. Because their unique oxygen chemistry and key role in drug xenobiotic metabolism, particular attention has been devoted elucidating mechanism substrate recognition. In this work, we analyzed three-dimensional structures a monomeric cytochrome P450 from Saccharopolyspora erythraea, commonly called EryK, binding kinetics to its ligand, erythromycin D. Three different...
We have obtained an experimental estimate of the free energy change associated with variations at interface between protein subunits, a subject that has raised considerable interest since concept accessible surface area was introduced by Lee and Richards [Lee, B. & Richards, F. M. (1971) J. Mol. Biol. 55, 379–400]. determined analytical ultracentrifugation dimer–tetramer equilibrium constant five single three double mutants human Hb. One mutation is stationary α 1 β interface, all others...
The structures of deoxy human haemoglobin and an artificial mutant (Tyrα42→His) have been solved at 120 K. While overall agreement between these others in the PDB is very good, certain side chains are found to be shifted, absent from electron-density map or different rotamers. Non-crystallographic symmetry (NCS) well obeyed native protein, but not around site changed residue mutant. NCS also by water molecule invariably α-chain haem pocket room-temperature crystal haemoglobin. At K, this...
Abstract Our aim is to shed light on the conservation of potential ligand docking sites that play an important role in dynamics globins by using technique filling internal cavities naturally present hemoglobin and myoglobin with xenon atoms. In particular, we high resolution structures Xe‐adduct deoxygenated wild type human a quadruple mutant (L(B10)Y H(E7)Q α β chains). For sake comparison also determined under same experimental conditions complex sperm whale myoglobin. The analysis...
X-ray absorption spectroscopy is exquisitely sensitive to the coordination geometry of an absorbing atom and therefore allows bond distances angles surrounding atomic cluster be measured with resolution. By contrast, accuracy resolution metalloprotein active sites obtainable from x-ray crystallography are often insufficient analyze electronic properties metals that essential for their biological functions. Here, we demonstrate combination both methods on same single crystal yields a...
Human ferritins have been extensively studied to be used as nanocarriers for diverse applications and could represent a convenient alternative targeted delivery of anticancer drugs imaging agents. However, the most relevant limitation their is need highly acidic experimental conditions during initial steps particle/cargo assembly, process that affect both drug stability complete reassembly ferritin cage. To overcome this issue unique assembly Archaeoglobus fulgidus was genetically engineered...
COVID-19 is a highly infectious disease caused by newly emerged coronavirus (SARS-CoV-2) that has rapidly progressed into pandemic. This unprecedent emergency stressed the significance of developing effective therapeutics to fight current and future outbreaks. The receptor-binding domain (RBD) SARS-CoV-2 surface Spike protein main target for vaccines represents helpful "tool" produce neutralizing antibodies or diagnostic kits. In this work, we provide detailed characterization native RBD...