Cryo-EM structure of antibacterial efflux transporter QacA in Staphylococcus aureus reveals a novel extracellular loop with allosteric role

ABSTRACT: Efflux of antibacterial compounds is a major mechanism for developing antimicrobial resistance. In the Gram-positive pathogen Staphylococcus aureus, QacA, a 14 transmembrane helix containing major facilitator superfamily antiporter, mediates proton-coupled efflux of mono and divalent cationic antibacterial compounds. In this study, we report the cryo-EM structure of QacA, with a single mutation D411N that improves homogeneity and retains efflux activity against divalent cationic compounds like dequalinium and chlorhexidine. The structure of substrate-free QacA, complexed to two single-domain camelid antibodies, was elucidated to a resolution of 3.6 Å. The structure displays an outward-open conformation with an extracellular helical hairpin loop (EL7) between transmembrane helices 13 and 14

SUBMITTER: Dr. Puja Majumder 

PROVIDER: S-SCDT-10_15252-EMBJ_2023113418 | biostudies-other |

REPOSITORIES: biostudies-other