Alessio Atzori

• PhD
• Research Associate at University of Cagliari

Peptidomimetics effective in modulating protein-protein interactions and resistant to proteolysis have potential in therapeutic applications. An appealing yet underperforming peptidomimetic strategy is to employ D-amino acids and reversed sequences to mimic a lead peptide conformation, either separately or as the combined retro-inverso peptide. In...

Protein plasticity, whilst often linked to biological function, also provides opportunities for rational design of selective and potent inhibitors of their function. The application of computational methods to predict concealed protein concavities is challenging, given that the motions involved can be significant and occur over long time scales. He...

The drug/proton antiporter AcrB, engine of the major efflux pump AcrAB(Z)-TolC of Escherichia coli and other bacteria, is characterized by its impressive ability to transport chemically diverse compounds, conferring a multi-drug resistance (MDR) phenotype. Although hundreds of small molecules are known to be AcrB substrates, only a few co-crystal s...

With the spreading of antibiotic resistance, the translocation of antibiotics through bacterial envelopes is crucial for their antibacterial activity. In Gram-negative bacteria, the interplay between membrane permeability and drug efflux pumps must be investigated as a whole. Here, we quantified the intracellular accumulation of a series of fluoroq...

Understanding the molecular determinants for recognition, binding and transport of antibiotics by multidrug efflux systems is important for basic research and useful for the design of more effective antimicrobial compounds. Imipenem and meropenem are two carbapenems whose antibacterial activity is known to be poorly and strongly affected by MexAB-O...

Efflux pump avoidance and inhibition are desired properties for the optimization of antibacterial activities against Gram-negative bacteria. However, molecular and physicochemical interactions defining the interface between compounds and efflux pumps remain poorly understood. We identified properties that correlate with efflux avoidance and inhibit...

Polymorphisms in the region of the calmodulin-dependent kinase isoform D (CaMK1D) gene are associated with increased incidence of diabetes, with the most common polymorphism resulting in increased recognition by transcription factors and increased protein expression. While reducing CaMK1D expression has a potentially beneficial effect on glucose pr...

The drug/proton antiporter AcrB, part of the major efflux pump AcrABZ-TolC in Escherichia coli, is characterized by its impressive ability to transport chemically diverse compounds, conferring a multi-drug resistance phenotype. However, molecular features differentiating between good and poor substrates of the pump have yet to be identified. In thi...

The putative mechanism by which bacterial RND-type multidrug efflux pumps recognize and transport their substrates is a complex and fascinating enigma of structural biology. How a single protein can recognize a huge number of unrelated compounds and transport them through one or just a few mechanisms is an amazing feature not yet completely unveile...

Nucleic acids are highly charged biopolymers whose secondary structure is strongly dependent on electrostatic interactions. Solvent molecules and ions are also believed to play an important role in mediating and directing both sequence recognition and interactions with other molecules, such as proteins and a variety of ligands. Therefore, to fully...

Figure S1. Replica exchange equilibration for the (initially) 270 K replica. Figure S2. 310 helical content from REMD simulations of WT, I, R and RI. Table S1. Average number of hydrogen bonds between the backbone peptide C = O of residues i and the backbone peptide NH of the residues i +4 and average total number of hydrogen bonds within sequence...

DNA is a highly charged polyanion, whose structure, flexibility and biological functionality are strongly influenced by the interactions with solvent and counterions. In recent years it has been shown that the monovalent cations, as the physiological counterions Na+ and K+ can bind directly to DNA, partially losing their hydration water. These stud...