Kumar, S and Athreya, A and Gulati, A and Nair, RM and Mahendran, I and Ranjan, R and Penmatsa, A (2021) Structural basis of inhibition of a transporter from Staphylococcus aureus, NorC, through a single-domain camelid antibody. In: Communications Biology, 4 (1).
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Abstract
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 à . 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. © 2021, The Author(s).
| Item Type: | Journal Article |
|---|---|
| Publication: | Communications Biology |
| Publisher: | Nature Research |
| Additional Information: | The copyright for this article belongs to Nature Research |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 09 Dec 2021 09:28 |
| Last Modified: | 09 Dec 2021 09:28 |
| URI: | http://eprints.iisc.ac.in/id/eprint/69580 |
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