Molecular dynamics in multidimensional space explains how mutations affect the association path of neomycin to a riboswitch.

Riboswitches are messenger RNA (mRNA) fragments binding specific small molecules to regulate gene expression. A synthetic N1 riboswitch, inserted into yeast mRNA controls the translation of a reporter gene in response to neomycin. However, its regulatory activity is sensitive to single-point RNA mutations, even those distant from the neomycin binding site.

Aromatic Diboronic Acids as Effective KPC/AmpC Inhibitors.

Over 30 compounds, including -, -, and -phenylenediboronic acids, -substituted phenylboronic acids, benzenetriboronic acids, di- and triboronated thiophenes, and pyridine derivatives were investigated as potential β-lactamase inhibitors. The highest activity against KPC-type carbapenemases was found for -phenylenediboronic acid , which at the concentration of 8/4 mg/L reduced carbapenems' MICs up to 16/8-fold, respectively. Checkerboard assays revealed strong synergy between carbapenems and with the fractional inhibitory concentrations indices of 0.

Structural dynamics influences the antibacterial activity of a cell-penetrating peptide (KFF)K.

Given the widespread demand for novel antibacterial agents, we modified a cell-penetrating peptide (KFF)K to transform it into an antibacterial peptide. Namely, we inserted a hydrocarbon staple into the (KFF)K sequence to induce and stabilize its membrane-active secondary structure. The staples were introduced at two positions, (KFF)K[5-9] and (KFF)K[2-6], to retain the initial amphipathic character of the unstapled peptide.

Mutations of N1 Riboswitch Affect its Dynamics and Recognition by Neomycin Through Conformational Selection.

Short, structured fragments of non-coding mRNA may act as molecular switches upon binding specific ligands, regulating the translation of proteins encoded downstream this mRNA sequence. One switch, called riboswitch N1, is regulated by aminoglycosides such as neomycin. Nucleobase mutations in the apical loop, although distant from the binding pocket, significantly affect neomycin affinity and riboswitch regulatory efficiency.