Characterisation of the selective binding of antibiotics vancomycin and teicoplanin by the VanS receptor regulating type A vancomycin resistance in the enterococci

A-type resistance towards "last-line" glycopeptide antibiotic vancomycin in the leading hospital acquired infectious agent, the enterococci, is the most common in the UK. Resistance is regulated by the VanRASA two-component system, comprising the histidine sensor kinase VanSA and the partner response regulator VanRA. The nature of the activating ligand for VanSA has not been identified, therefore this work sought to identify and characterise ligand(s) for VanSA. In vitro approaches were used to screen the structural and activity effects of a range of potential ligands with purified VanSA protein. Of the screened ligands (glycopeptide antibiotics vancomycin and teicoplanin, and peptidoglycan components N-acetylmuramic acid, D-Ala-D-Ala and Ala-D-y-Glu-Lys-D-Ala-D-Ala) only glycopeptide antibiotics vancomycin and teicoplanin were found to bind VanSA with different affinities (vancomycin 70 μM; teicoplanin 30 and 170 μM), and were proposed to bind via exposed aromatic residues tryptophan and tyrosine. Furthermore, binding of the antibiotics induced quicker, longer-lived phosphorylation states for VanSA, proposing them as activators of type A vancomycin resistance in the enterococci. [Abstract copyright: Copyright © 2017. Published by Elsevier B.V.

MAGNETIC CIRCULAR DICHROISM OF THE SINGLET n−Π∗n-\Pi^{*} TRANSITION OF SATURATED KETONES: CALCULATION OF STRUCTURAL EFFECTS FOR METHYLCYCLOHEXANONES

Author Institution: Department of Chemistry, Stanford UniversityThe structural part of the MCD of the $n-\Pi^{*}$ transition for equatorially substituted methyl cyclohexanones have been calculated using CNDO/S wave functions. The calculated magnetic rotational strengths are in reasonable agreement with experimental values referenced to cyclohexanone. These results are interpreted in terms of permanent moments and the variations in the transition moment parallel to the lone pair orbital. The connection between vibrational analysis and the MCD spectra of ketones and the origin dependence problem are to be discussed briefly