Roles of inter- and intramolecular tryptophan interactions in membrane-active proteins revealed by racemic protein crystallography.

ABSTRACT: Tryptophan is frequently found on the surface of membrane-associated proteins that interact with the lipid membrane. However, because of their multifaceted interactions, it is difficult to pinpoint the structure-activity relationship of each tryptophan residue. Here, we describe the use of racemic protein crystallography to probe dedicated tryptophan interactions of a model tryptophan-rich bacteriocin aureocin A53 (AucA) by inclusion and/or exclusion of potential ligands. In the presence of tetrahedral anions that are isosteric to the head group of phospholipids, distinct tryptophan H-bond networks were revealed. H-bond donation by W40 was critical for antibacterial activity, as its substitution by 1-methyltryptophan resulted in substantial loss of activity against bacterial clinical isola

SUBMITTER: Lander AJ 

PROVIDER: S-EPMC10354048 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature