A5030303785- Helicobacter pylori-related gastroenterology studies
- Enzyme Structure and Function
- Antibiotic Resistance in Bacteria
- Tuberculosis Research and Epidemiology
- Photosynthetic Processes and Mechanisms
- Galectins and Cancer Biology
- Chemical Synthesis and Analysis
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Veterinary medicine and infectious diseases
- Cellular transport and secretion
- Enzyme Catalysis and Immobilization
- Chemical Reactions and Isotopes
- Bacterial Genetics and Biotechnology
- Endoplasmic Reticulum Stress and Disease
- Antibiotics Pharmacokinetics and Efficacy
- Porphyrin Metabolism and Disorders
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- Amino Acid Enzymes and Metabolism
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Freezing and Crystallization Processes
- Protein Structure and Dynamics
- Trace Elements in Health
- Microbial Natural Products and Biosynthesis
- Pneumocystis jirovecii pneumonia detection and treatment
University of Padua
2016-2025
Veneto Institute of Molecular Medicine
2004-2013
Istituto di Chimica Biomolecolare
2004-2009
Argonne National Laboratory
2005
From a large combinatorial library of chemically constrained bicyclic peptides we isolated selective and potent (K(i) = 53 nM) inhibitor human urokinase-type plasminogen activator (uPA) crystallized the complex. This revealed an extended structure peptide with both loops engaging target to form interaction surface 701 Å(2) multiple hydrogen bonds complementary charge interactions, explaining high affinity specificity inhibitor. The interface resembles that between two proteins suggests these...
Plant organelle function must constantly adjust to environmental conditions, which requires dynamic coordination. Ca(2+) signaling may play a central role in this process. Free dynamics are tightly regulated and differ markedly between the cytosol, plastid stroma, mitochondrial matrix. The mechanistic basis of compartment-specific is poorly understood. Here, we studied At-MICU, an EF-hand protein Arabidopsis thaliana with homology constituents uniporter machinery mammals. MICU binds...
The serine protease inhibitor SerpinB3 has been described as critical mediator of liver fibrosis and it recently proposed an additional hepatokine involved in NASH development insulin resistance. Protease Activated Receptor 2 identified a novel regulator hepatic metabolism. A targeted therapeutic strategy for investigated, using 1-Piperidine Propionic Acid (1-PPA), since this compound both inhibitor. effect on inflammation genes was assessed human macrophage stellate cell lines. Transgenic...
The current trend dealing with the production of per- and polyfluoroalkyl substances (PFASs) involves shifting toward branched short-chain fluorinated compounds known as new-generation PFASs. A key aspect to be clarified, address adverse health effects associated exposure PFASs, is their binding mode human serum albumin (hSA), most abundant protein in plasma. In this study, we investigated interaction between hSA two representative namely, HPFO-DA C6O4. In-solution studies revealed that both...
Abstract Selective removal of dysfunctional mitochondria via autophagy is crucial for the maintenance cellular homeostasis. This event initiated by translocation E3 ubiquitin ligase Parkin to damaged mitochondria, and it requires Serine/Threonine-protein kinase PINK1. In a coordinated set events, PINK1 operates upstream in linear pathway that leads phosphorylation Parkin, Ubiquitin, mitochondrial substrates, promote ubiquitination outer membrane proteins. Ubiquitin-decorated are selectively...
Macrocycles offer an attractive format for drug development due to their good binding properties and potential cross cell membranes. To efficiently identify macrocyclic ligands new targets, methods the synthesis screening of large combinatorial libraries small cyclic peptides were developed, many them using thiol groups efficient peptide macrocyclization. However, a weakness these is that invariant thiol-containing building blocks such as cysteine are used, resulting in region does not...
CK2 is a highly pleiotropic Ser/Thr protein kinase that able to promote cell survival and enhance the tumour phenotype under specific circumstances. We have determined crystal structure of three new complexes with tetrabromobenzimidazole derivatives display K(i) values between 0.15 0.30 microM. A comparative analysis these data those four other inhibitors same family revealed presence some conserved water molecules in ATP-binding site. These waters reside near Lys68, an area positive...
Abstract Perfluorooctanoic acid (PFOA) is a toxic compound that absorbed and distributed throughout the body by noncovalent binding to serum proteins such as human albumin (hSA). Though interaction between PFOA hSA has been already assessed using various analytical techniques, high resolution detailed analysis of mode still lacking. We report here crystal structure in complex with medium‐chain saturated fatty (FA). A total eight distinct sites, four occupied PFOAs FAs, have identified. In...
Abstract Macrocycles have excellent potential as therapeutics due to their ability bind challenging targets. However, generating macrocycles against new targets is hindered by a lack of large macrocycle libraries for high-throughput screening. To overcome this, we herein established combinatorial approach tethering myriad chemical fragments peripheral groups structurally diverse macrocyclic scaffolds in fashion, all at picomole scale nanoliter volumes using acoustic droplet ejection...
Antimicrobial resistance poses a severe threat to human health and Pseudomonas aeruginosa stands out among the pathogens responsible for this emergency. The SOS response DNA damage is crucial in bacterial evolution, influencing development adaptability challenging environments, especially under antibiotic exposure. Recombinase A (RecA) transcriptional repressor LexA are key players that orchestrate process, determining either silencing or active transcription of genes their control. By...
Bacterial resistance has become a worldwide concern after the emergence of metallo-β-lactamases (MBLs). They represent one major mechanisms bacterial against beta-lactam antibiotics. Among MBLs, New Delhi metallo-β-lactamase-1 NDM-1, most prevalent type, is extremely efficient in inactivating nearly all-available antibiotics including last resort carbapenems. No inhibitors for NDM-1 are currently available therapy, making spread producing strains serious menace. With this perspective, we...
An efficient cyclization reaction allows for screening of large macrocycle libraries and yields a potent thrombin inhibitor.
The hydrolytic cleavage of the hydantoin ring allantoin, catalyzed by allantoinase, is required for utilization nitrogen present in purine-derived compounds. allantoinase gene (DAL1), however, missing many completely sequenced organisms able to use allantoin as a source. Here we show that an alternative (puuE) can be precisely identified analyzing its logic relationship with three other genes pathway. novel annotated structure and sequence data bases polysaccharide deacetylase homology...
Human transthyretin (TTR) is an amyloidogenic protein whose mild amyloidogenicity enhanced by many point mutations affecting considerably the amyloid disease phenotype. To ascertain whether high potential of TTR variants may be explained on basis conformational change hypothesis, aim this work was to determine structural alterations for five crystallized under native and/or destabilizing (moderately acidic pH) conditions. While at pH changes more significant because a higher local...