Structural basis of inhibition of a transporter from Staphylococcus aureus, NorC, through a single-domain camelid antibody.

Publication Type:

Journal Article


Commun Biol, Volume 4, Issue 1, p.836 (2021)


<p>Transporters play vital roles in acquiring antimicrobial resistance among pathogenic bacteria. In this study, we report the X-ray structure of NorC, a 14-transmembrane major facilitator superfamily member that is implicated in fluoroquinolone resistance in drug-resistant Staphylococcus aureus strains, at a resolution of 3.6&thinsp;Å. The NorC structure was determined in complex with a single-domain camelid antibody that interacts at the extracellular face of the transporter and stabilizes it in an outward-open conformation. The complementarity determining regions of the antibody enter and block solvent access to the interior of the vestibule, thereby inhibiting alternating-access. NorC specifically interacts with an organic cation, tetraphenylphosphonium, although it does not demonstrate an ability to transport it. The interaction is compromised in the presence of NorC-antibody complex, consequently establishing a strategy to detect and block NorC and related transporters through the use of single-domain camelid antibodies.</p>

NorC WT and NorC-K398A are deposited in the Protein Data Bank with PDB IDs 7D5P and 7D5Q