A5000822828- Protein Tyrosine Phosphatases
- Protein Structure and Dynamics
- Hemoglobin structure and function
- ATP Synthase and ATPases Research
- Galectins and Cancer Biology
- Protein Kinase Regulation and GTPase Signaling
- Neonatal Health and Biochemistry
- Heme Oxygenase-1 and Carbon Monoxide
- Erythrocyte Function and Pathophysiology
- Enzyme Structure and Function
- Spectroscopy and Quantum Chemical Studies
- RNA and protein synthesis mechanisms
- Genomics, phytochemicals, and oxidative stress
- Sphingolipid Metabolism and Signaling
- Medicinal plant effects and applications
- Oropharyngeal Anatomy and Pathologies
- thermodynamics and calorimetric analyses
- Skin and Cellular Biology Research
- Supramolecular Self-Assembly in Materials
- Cell Adhesion Molecules Research
- Biochemical and Structural Characterization
- Plant Pathogenic Bacteria Studies
- melanin and skin pigmentation
- Cerebrovascular and genetic disorders
- Molecular Junctions and Nanostructures
Saarland University
2020-2024
University of Göttingen
2018-2021
University of Rome Tor Vergata
2014-2020
Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di Frascati
2018
École Polytechnique Fédérale de Lausanne
2018
Istituto di Nanotecnologia
2018
Université de Rennes
2018
Institut de Physique de Rennes
2018
Centre National de la Recherche Scientifique
2018
Technische Universität Dresden
2014-2015
Transcription factors operate in developmental processes to mediate inductive events and cell competence, perturbation of their function or regulation can dramatically affect morphogenesis, organogenesis, growth. We report that a narrow spectrum amino-acid substitutions within the transactivation domain v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF), leucine zipper-containing transcription factor AP1 superfamily, profoundly development. Seven different de novo missense...
Sulfated glycosaminoglycans (GAGs) can direct cellular processes by interacting with proteins of the extracellular matrix (ECM). In this study we characterize interaction profiles chemically sulfated hyaluronan (HA) and chondroitin sulfate (CS) derivatives bone morphogenetic protein-2 (BMP-2) investigate their relevance for complex formation receptor BMPR-IA. These goals were addressed surface plasmon resonance (SPR) ELISA in combination molecular modeling dynamics simulation. We found not...
Germline mutations in PTPN11, the gene encoding Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder. Here, we report on identification of five different PTPN11 missense changes affecting residues Leu261 , Leu262 and Arg265 16 unrelated individuals with clinical diagnosis NS or features suggestive for this disorder, specifying novel disease-causing mutation cluster. Expression...
Abstract SHP2 is a protein tyrosine phosphatase (PTP) involved in multiple signaling pathways. Mutations of can result Noonan syndrome or pediatric malignancies. Inhibition wild-type represents novel strategy against several cancers. activated by binding phosphopeptide to the N-SH2 domain SHP2, thereby favoring dissociation and exposing active site on PTP domain. The conformational transitions controlling ligand affinity remain poorly understood. Using molecular simulations, we revealed an...
Oxidative stress is a widespread challenge for living organisms, and especially so parasitic ones, given the fact that their hosts can produce reactive oxygen species (ROS) as mechanism of defense. Thus, long lived parasites, such flatworm Schistosomes, have evolved refined enzymatic systems capable detoxifying ROS. Among these, glutathione peroxidases (Gpx) are family sulfur or selenium-dependent isozymes sharing ability to reduce peroxides using reducing equivalents provided by possibly...
SH2 domain-containing tyrosine phosphatase 2 (SHP2), encoded by PTPN11, plays a fundamental role in the modulation of several signaling pathways. Germline and somatic mutations PTPN11 are associated with different rare diseases hematologic malignancies, recent studies have individuated SHP2 as central node oncogenesis cancer drug resistance. The structure includes two Src homology domains (N-SH2 C-SH2) followed catalytic protein (PTP) domain. Under basal conditions, N-SH2 domain blocks...
SHP2 is a tyrosine phosphatase that plays regulatory role in multiple intracellular signaling cascades and known to be oncogenic certain contexts. In the absence of effectors, adopts an autoinhibited conformation with its N-SH2 domain blocking active site. Given key regulating SHP2, this has been extensively studied, often by X-ray crystallography. Using combination structural analyses molecular dynamics (MD) simulations we show crystallographic environment can significantly influence...
In this paper we extend the perturbed matrix method by explicitly including nuclear degrees of freedom, in order to treat quantum vibrational states a molecule. previous showed how include, simple way, freedom for calculation molecular polarizability. present work and generalize approach model vibroelectronic transitions, requiring more sophisticated treatment.
Neuroglobin (Ngb) is a globular protein that reversibly binds small ligands at the six coordination position of heme. With respect to other globins similar myoglobin, Ngb displays some peculiarities as topological reorganization internal cavities coupled sliding heme, or binding endogenous distal histidine heme in absence an exogenous ligand. In this Article, by using multiple (independent) molecular dynamics trajectories (about 500 ns total), migration pathways photolized carbon monoxide...
We have determined the heterogeneous structural ensemble of tandem SH2 domains protein tyrosine phosphatase SHP2 in agreement with experimental data from small-angle X-ray scattering and NMR residual dipolar couplings solution.
The effect of structural disorder on the X-ray absorption near-edge structure (XANES) spectrum a heme protein has been investigated using dynamical description system derived from molecular dynamics (MD) simulations. XANES spectra neuroglobin (Ngb) and carbonmonoxy-neuroglobin (NgbCO) have quantitatively reproduced, starting MD geometrical configurations, without carrying out any optimization in parameter space. These results provide an important experimental validation reliability...
A detailed characterization of a host−guest supramolecular copolymer, formed by adamantane and β-cyclodextrin dimers (Ad2 βCD2, respectively) in aqueous solution, has been carried out combining small-angle X-ray scattering light experiments with molecular dynamics (MD) Monte Carlo (MC) simulations. First, the solutions monomers were studied straightforward analysis data. Afterward, complex given Ad2 two molecules was investigated correlating results MD simulations, to characterize linkage....
Significance SHP2 is a multidomain protein, playing an important role in upregulating cellular processes such as cell survival, proliferation, and programmed death. mutations cause developmental disorders are found many cancer types, including neuroblastoma, breast cancer, leukemia. In healthy cells, mainly takes autoinhibited, inactive form, activated upon binding of phosphopeptides to the N-SH2 domain. For past two decades, widening cleft peptide has been considered key event driving...
Infrared temperature-dependent spectroscopy is a well-known tool to characterize folding/unfolding transitions in peptides and proteins, assuming that the higher temperature, unfolded population. The infrared spectra at different temperatures of two β-hairpin (gramicidin S analogues GS6 GS10) are here reconstructed by means molecular dynamics (MD) simulations theoretical-computational method based on perturbed matrix method. calculated result good agreement with experimental available...
Primrose syndrome (PS) is a rare disorder characterized by macrocephaly, tall stature, intellectual disability, autistic traits, and disturbances of glucose metabolism with insulin-resistant diabetes distal muscle wasting occurring in adulthood. The caused functional dysregulation ZBTB20, transcriptional repressor controlling energetic developmental programs. ZBTB20 maps genomic region that deleted the 3q13.31 microdeletion syndrome, which explains clinical overlap between two disorders. A...
Abstract Neuroglobin (Ngb) is predominantly expressed in neurons of the central and peripheral nervous systems it clearly seems to be involved neuroprotection. Engineering Ngb observe structural dynamic alterations associated with perturbation ligand binding might reveal important determinants, could shed light on key features related its mechanism action. Our results highlight relevance CD loop Phe106 as distal proximal controls murine neuroglobin. We observed effects individual combined...