A5032530579- Synthetic Organic Chemistry Methods
- Microbial Natural Products and Biosynthesis
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Marine Sponges and Natural Products
- X-ray Diffraction in Crystallography
- Mycobacterium research and diagnosis
- RNA and protein synthesis mechanisms
- Crystallization and Solubility Studies
- Tuberculosis Research and Epidemiology
- Neuroscience and Neuropharmacology Research
- Metabolomics and Mass Spectrometry Studies
- Asymmetric Synthesis and Catalysis
- Chronic Myeloid Leukemia Treatments
- Ion channel regulation and function
- Cancer, Hypoxia, and Metabolism
- Lipid Membrane Structure and Behavior
- Bacteriophages and microbial interactions
- Chronic Lymphocytic Leukemia Research
- Photosynthetic Processes and Mechanisms
- Oxidative Organic Chemistry Reactions
- Metal-Catalyzed Oxygenation Mechanisms
- Advanced Proteomics Techniques and Applications
- Trace Elements in Health
- Bacterial Genetics and Biotechnology
University of Florence
2020-2024
University of Campania "Luigi Vanvitelli"
2024
Institute of Crystallography
2024
National Research Council
2024
Maastricht University
2016-2021
European Molecular Biology Laboratory
2013-2018
Nanyang Technological University
2015-2016
Deutsches Elektronen-Synchrotron DESY
2015
Universität Hamburg
2013-2014
European Molecular Biology Laboratory
2012-2014
New developments in the program package
Dynamic ensembles of macromolecules mediate essential processes in biology. Understanding the mechanisms driving function and molecular interactions 'unstructured' flexible molecules requires alternative approaches to those traditionally employed structural Small-angle X-ray scattering (SAXS) is an established method for characterization biological solution, directly applicable study systems such as intrinsically disordered proteins multi-domain with unstructured regions. The Ensemble...
There are two ways about it: One route to the potent antibiotic (−)-platensimycin used a catalytic asymmetric cycloisomerization and other an auxiliary-controlled alkylation set configuration at key chiral center (see scheme, TMS=trimethylsilyl). This latter synthesis also oxidative dearomatization step construct spirocyclic intermediate en natural product.
Platensimycin is the flagship member of a new and growing class antibiotics with promising antibacterial properties against drug-resistant bacteria. The total syntheses platensimycin its congeners, platensimycins B1 B3, platensic acid, methyl platensinoate, platensimide A, homoplatensimide A ester, are described. convergent strategy developed toward these target molecules involved construction their cage-like core followed by attachment various side chains through amide bond formation. In...
Graphical Abstract The asymmetric total synthesis of the newly discovered and potent antibiotic platencin has been achieved. approach makes use an Diels–Alder reaction, a gold(I)-catalyzed cyclization, homoallyl radical rearrangement to forge polycyclic architecture this intriguing target (see scheme, SEM=2-(trimethylsilyl)ethoxymethyl).
The molecular design, chemical synthesis, and biological evaluation of two distinct series platensimycin analogues with varying degrees complexity are described. first compounds probes the importance benzoic acid subunit molecule, while second explores tetracyclic cage domain. data obtained reveal that, substituted domain is a highly conserved structural motif within active strict functional group requirements, molecule can tolerate considerable modifications without losing action. These...
The secondary metabolites platensimycin and platencin, isolated from the bacterial strain Streptomyces platensis, represent a novel class of natural products exhibiting unique potent antibacterial activity. Platencin, though structurally similar to platensimycin, has been found operate through slightly different mechanism action involving dual inhibition lipid elongation enzymes FabF FabH. Both exhibit strong, broad-spectrum, gram-positive activity key antibiotic resistant strains, including...
RNA can directly control protein activity in a process called riboregulation; only few mechanisms of riboregulation have been described detail, none which characterized on structural grounds. Here, we present comprehensive structural, functional, and phylogenetic analysis cytosolic serine hydroxymethyltransferase (SHMT1), the enzyme interconverting glycine one-carbon metabolism. We determined cryoelectron microscopy (cryo-EM) structure human SHMT1 its free- RNA-bound states, show that...
Zwei Wege führen zum Ziel – dem hochwirksamen Antibiotikum (−)-Platensimycin: eine katalytische asymmetrische Cycloisomerisierung oder auxiliargesteuerte Alkylierung zur Festlegung der Konfiguration eines wichtigen Chiralitätszentrums (siehe Schema, TMS=Trimethylsilyl). In zweiten Synthese wird ein spirocyclisches Schlüsselintermediat auf Weg Naturstoff durch oxidative Desaromatisierung erzeugt.
Gephyrin is a trimeric protein involved in the final steps of molybdenum-cofactor (Moco) biosynthesis and clustering inhibitory glycine GABA A receptors at postsynaptic specializations. Each protomer consists stably folded domains (referred to as G E domains) located either terminus connected by proteolytically sensitive linker ∼150 residues. Both terminal can oligomerize their isolated forms; however, context full-length only G-domain trimer permanently present, whereas E-domain...
Infection by the four serotypes of Dengue virus (DENV-1 to DENV-4) causes an important arthropod-borne viral disease in humans. The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication RNA harbours a methyltransferase (MTase) domain RNA-dependent polymerase (RdRp) domain. In this study, insights into overall structure flexibility entire NS5 all solution are presented first time. models derived revealed arrangement full-length (NS5FL) proteins with MTase...
Although solubilization of lipid membranes has been studied extensively, questions remain regarding the structural pathways and metastable structures involved. This study investigated whether non-ionic detergent Triton X-100 follows classical pathway or if intermediate nanostructures are formed.Small angle X-ray neutron scattering (SAXS/SANS) was used in combination with transmission electron cryo-microscopy cryo-tomography to deduce structure mixtures...
Ein Antibiotikum aus dem Erdreich: Bei der asymmetrischen Totalsynthese des kürzlich entdeckten, stark antibiotischen Platencin wird das komplexe polycyclische System durch eine asymmetrische Diels-Alder-Reaktion, Gold(I)-katalysierte Cyclisierung und radikalische Homoallylumlagerung aufgebaut (siehe Schema, SEM = 2-(Trimethylsilyl)ethoxymethyl).
Glutaminase C is a key metabolic enzyme, which unregulated in many cancer systems and believed to play central role the Warburg effect, whereby cells undergo changes an altered profile. A long-standing hypothesis links enzymatic activity protein oligomeric state, hence study of solution behavior general oligomer state particular glutaminase important for understanding mechanism activation inhibition. In this report, extensively investigated correlation enzyme concentration or phosphate...
Abstract Using SAXS and NMR spectroscopy, we herein provide a high-resolution description of the intrinsically disordered N-terminal domain (PNT, aa 1–406) shared by Nipah virus (NiV) phosphoprotein (P) V protein, two key players in viral genome replication evasion host innate immune response, respectively. The use multidimensional spectroscopy allowed us to assign as much 91% residues this whose size constitutes technical challenge for studies. Chemical shifts nuclear relaxation...
ESX-1 is a major virulence factor of Mycobacterium tuberculosis, secretion machinery directly involved in the survival microorganism from immune system defence. It disrupts phagosome membrane host cell through contact-dependent mechanism. Recently, structure inner-membrane core complex homologous ESX-3 and ESX-5 was resolved; however, elements outer or those acting on are unknown. Protein substrates might form this missing element. Here, we describe oligomerisation process substrate EspB,...
Casitas B-lineage lymphoma (Cbl or c-Cbl) is a RING ubiquitin ligase that negatively regulates protein tyrosine kinase (PTK) signalling. Phosphorylation of conserved residue (Tyr371) on the linker helix region (LHR) between substrate-binding and domains required to ubiquitinate PTKs, thereby flagging them for degradation. This Tyr mutational hotspot in myeloproliferative neoplasms. Previous studies have revealed select point mutations Tyr371 can potentiate transformation cells mice but not...
At present, 51 genes are already known to be responsible for Non-Syndromic hereditary Hearing Loss (NSHL), but the knowledge of 121 NSHL-linked chromosomal regions brings hypothesis that a number disease have still uncovered. To help scientists find new NSHL genes, we built gene-scoring system, integrating Gene Ontology, NCBI and Map Viewer databases, which prioritizes candidate according their probability cause NSHL. We defined set candidates measured functional similarity with respect gene...