7D5P

Structure of NorC transporter in an outward-open conformation in complex with a single-chain Indian camelid antibody

Summary for 7D5P

• Entry DOI: 10.2210/pdb7d5p/pdb
• Descriptor: Drug transporter, putative, ICab, ZINC ION (3 entities in total)
• Functional Keywords: norc, major facilitator superfamily, transporter, outward-open, membrane protein
• Biological source: Staphylococcus aureus subsp. aureus COL; More
• Total number of polymer chains: 4
• Total formula weight: 132067.16

Authors

Kumar, S.,Athreya, A.,Penmatsa, A. (deposition date: 2020-09-27, release date: 2021-06-09, Last modification date: 2024-10-09)

Primary citation

Kumar, S.,Athreya, A.,Gulati, A.,Nair, R.M.,Mahendran, I.,Ranjan, R.,Penmatsa, A.
Structural basis of inhibition of a transporter from Staphylococcus aureus, NorC, through a single-domain camelid antibody.
Commun Biol, 4:836-836, 2021

PubMed 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 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.

PubMed: 34226658
DOI: 10.1038/s42003-021-02357-x

Experimental method

X-RAY DIFFRACTION (3.65 Å)