A5078760925- Protein Structure and Dynamics
- Heat shock proteins research
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Antimicrobial Resistance in Staphylococcus
- thermodynamics and calorimetric analyses
- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- Computational Drug Discovery Methods
- Insect Resistance and Genetics
- RNA Research and Splicing
- Bacterial biofilms and quorum sensing
- Advanced NMR Techniques and Applications
- Machine Learning in Bioinformatics
- Ubiquitin and proteasome pathways
- Trace Elements in Health
- Cancer Research and Treatments
- Archaeology and ancient environmental studies
- Endoplasmic Reticulum Stress and Disease
- Click Chemistry and Applications
- Hepatitis B Virus Studies
- Cultural Heritage Materials Analysis
- Insect Pest Control Strategies
- Genomics, phytochemicals, and oxidative stress
- Muon and positron interactions and applications
University of South Florida
2013-2024
University of Tampa
2018
Goethe University Frankfurt
2013
Rutgers, The State University of New Jersey
2006-2009
University of Florence
2003-2004
National Centre of Scientific Research "Demokritos"
2003-2004
University of Sassari
2004
The conformational space sampled by the two-domain protein calmodulin has been explored an approach based on four sets of NMR observables obtained Tb 3+ - and Tm -substituted proteins. are pseudocontact shifts residual dipolar couplings C-terminal domain when lanthanide substitution is at N-terminal domain. Each set provides independent information conformations experienced molecule. It found that not all sterically allowed equally populated. Taking as reference, preferentially resides in a...
Complex conformational dynamics are essential for function of the dimeric molecular chaperone heat shock protein 90 (Hsp90), including transient, ATP-biased N-domain dimerization that is necessary to attain ATPase competence. The intrinsic, but weak, ATP hydrolyzing activity human Hsp90 markedly enhanced by co-chaperone Aha1. However, cellular concentration Aha1 substoichiometric relative Hsp90. Here we report initial recruitment this cochaperone phosphorylation a highly conserved tyrosine...
In the Firmicutes phylum, GpsB is a membrane associated protein that coordinates peptidoglycan synthesis with cell growth and division. Although has been studied in several bacteria, structure, function, interactome of Staphylococcus aureus largely uncharacterized. To address this knowledge gap, we solved crystal structure N-terminal domain S. GpsB, which adopts an atypical, asymmetric dimer, demonstrates major conformational flexibility can be mapped to hinge region formed by three-residue...
Abstract During the Hsp90-mediated chaperoning of protein kinases, core components machinery, Hsp90 and cochaperone Cdc37, recycle between different phosphorylation states that regulate progression chaperone cycle. We show Cdc37 at Y298 results in partial unfolding C-terminal domain population folding intermediates. Unfolding facilitates Y197 by unmasking a phosphopeptide sequence, which serves as docking site to recruit non-receptor tyrosine kinases complex via their SH2 domains. In turn,...
The possibility of selectively substituting one or more lanthanides into the four canonical calcium binding sites calcium-loaded vertebrate calmodulin (CaM) was investigated by monitoring changes in 1H-15N HSQC NMR spectra 15N-enriched protein upon titration with Yb3+. affinity for both N-terminal I and II is only moderately higher than that calcium, comparable two C-terminal sites. This situation induces to other noncanonical located at interdomain linker, N- ends, inter-EF-hand linkers....
Gram-negative bacteria expressing class A β-lactamases pose a serious health threat due to their ability inactivate all β-lactam antibiotics. The acyl–enzyme intermediate is central milestone in the hydrolysis reaction catalyzed by these enzymes. However, protonation states of catalytic residues this complex have never been fully analyzed experimentally inherent difficulties. To help unravel ambiguity surrounding β-lactamase catalysis, we used ultrahigh-resolution X-ray crystallography and...
Molecular chaperones have an essential role for the maintenance of a balanced protein homeostasis. Here, we investigate how kinases are recruited and loaded to Hsp90-Cdc37 complex, first step during Hsp90-mediated chaperoning that leads enhanced client kinase stability activation. We show conformational dynamics all partners is critical feature underlying loading mechanism. The kinome co-chaperone Cdc37 exists primarily in dynamic extended conformation but samples low-populated, well-defined...
Abstract Treatment with β-lactam antibiotics, particularly cephalosporins, is a major risk factor for Clostridioides difficile infection. These broad-spectrum antibiotics irreversibly inhibit penicillin-binding proteins (PBPs), which are serine-based enzymes that assemble the bacterial cell wall. However, C. has four different PBPs (PBP1-3 and SpoVD) various roles in growth spore formation, their specific links to resistance this pathogen underexplored. Here, we show PBP2 (known be essential...
The overexpression of atypical protein kinase C-iota (PKC-ι) is a biomarker for carcinogenesis in various cells, such as glioma, ovarian, renal, etc. manifesting potential drug target. In previous vitro studies, ICA-1S and ICA-1T, an experimental candidate inhibiting PKC-ι, has demonstrated its specificity promising efficacy against cancer cell types. Moreover, the vivo studies have low toxicity levels acute chronic murine models. Despite these prior developments, binding affinities...
The development of analytical research in recent decades, at the edge between chemistry and archaeology, provides new methods for study organic residues that are usually highly sensitive to natural decay.
The 2nd International Symposium on the Chaperone Code took place October 26-28, 2023 at Hilton Alexandria Old Town, VA, USA. event featured more than 100 attendees from ten countries and provided a dynamic platform for established researchers, emerging investigators, postdoctoral fellows, students to share insights ideas diverse facets of molecular chaperones with strong focus their regulation by post-translational modifications. format fostered discussions collaboration among participants....
Novologues KU-32 and KU-596 bind at the C-terminal domain of Hsp90 exploit a long-range allosteric network to modulate chaperone cycle.
The growing issue of insecticide resistance has meant the identification novel targets never been more important. Arylalkylamine N-acyltransferases (AANATs) have suggested as a potential new target. These promiscuous enzymes are involved in N-acylation biogenic amines to form N-acylamides. In insects, this process is key step melanism, hardening cuticle, removal amines, and biosynthesis fatty acid amides. unique nature each AANAT isoform characterized indicates organism accommodates an...
Abstract Bacterial cell division is a tightly regulated process that requires the formation of dynamic multi-protein complex. In Firmicutes phylum, GpsB membrane associated protein coordinates peptidoglycan synthesis for growth and division. Although has been studied in several organisms, structure, function, interactome Staphylococcus aureus largely uncharacterized, despite being reported as uniquely essential this clinically relevant bacterium. To address knowledge gap, we solved crystal...
The transfer of an acetyl group from acetyl-CoA to acceptor amine is a ubiquitous biochemical transformation catalyzed by Gcn5-related N-acetyltransferases (GNATs). Although it established that the reaction proceeds through sequential ordered mechanism, role in driving formation binary and ternary complexes remains elusive. Herein, we show CoA alter conformation substrate binding site arylalkylamine N-acetyltransferase (AANAT) facilitate interaction with substrates. However, presence within...
In the case of oxidized plastocyanin from Synechocystis sp. PCC6803, an NMR approach based on classical two and three dimensional experiments for sequential assignment leaves unobserved 14 out 98 amino acids. A protocol which simply makes use tailored versions 2D HSQC 3D CBCA(CO)NH CBCANH leads to identification nine above residues. The proposed differs previous aproaches in that it does not involve unconventional designed specifically paramagnetic systems, exploit occurrence a corresponding...