A key n??* Interaction in N-acyl homoserine lactones.

ABSTRACT: Many Gram-negative bacteria employ N-acyl homoserine lactones (AHLs) as signal molecules for quorum sensing. The binding of AHLs to their target LuxR-type receptor proteins can effect changes in growth, virulence, and other phenotypes. LuxR-type receptors therefore present attractive pharmaceutical targets for control of bacterial pathogenesis. Here, we present X-ray crystallographic and computational evidence that the conformation of free AHLs is biased away from the conformation observed when bound to their cognate receptor due to the influence of an n??* interaction. In this n??* interaction, the p-type lone pair (n) of the N-acyl oxygen overlaps with the ?* orbital of the lactone carbonyl group. This overlap results in the release of approximately 0.64 kcal/mol of energy. We also show that this interaction can be attenuated by installing electron-withdrawing groups on the N-acyl chain. Modulating this previously unappreciated interaction could present a new avenue toward effective inhibitors of bacterial quorum sensing.

SUBMITTER: Newberry RW 

PROVIDER: S-EPMC4219647 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature