5KCB

The structure of SAV2435 bound to ethidium bromide

Summary for 5KCB

• Entry DOI: 10.2210/pdb5kcb/pdb
• Related: 5KAT 5KAU 5KAV 5KAW 5KAX
• Descriptor: SA2223 protein, ETHIDIUM, SULFATE ION, ... (4 entities in total)
• Functional Keywords: gyri-like domatin, multi-drug recognition, unknown function
• Biological source: Staphylococcus aureus (strain N315)
• Total number of polymer chains: 1
• Total formula weight: 19350.74

Authors

Moreno, A.,Wade, H. (deposition date: 2016-06-06, release date: 2016-08-24, Last modification date: 2024-10-30)

Primary citation

Moreno, A.,Froehlig, J.R.,Bachas, S.,Gunio, D.,Alexander, T.,Vanya, A.,Wade, H.
Solution Binding and Structural Analyses Reveal Potential Multidrug Resistance Functions for SAV2435 and CTR107 and Other GyrI-like Proteins.
Biochemistry, 55:4850-4863, 2016

PubMed Abstract: Multidrug resistance (MDR) refers to the acquired ability of cells to tolerate a broad range of toxic compounds. One mechanism cells employ is to increase the level of expression of efflux pumps for the expulsion of xenobiotics. A key feature uniting efflux-related mechanisms is multidrug (MD) recognition, either by efflux pumps themselves or by their transcriptional regulators. However, models describing MD binding by MDR effectors are incomplete, underscoring the importance of studies focused on the recognition elements and key motifs that dictate polyspecific binding. One such motif is the GyrI-like domain, which is found in several MDR proteins and is postulated to have been adapted for small-molecule binding and signaling. Here we report the solution binding properties and crystal structures of two proteins containing GyrI-like domains, SAV2435 and CTR107, bound to various ligands. Furthermore, we provide a comparison with deposited crystal structures of GyrI-like proteins, revealing key features of GyrI-like domains that not only support polyspecific binding but also are conserved among GyrI-like domains. Together, our studies suggest that GyrI-like domains perform evolutionarily conserved functions connected to multidrug binding and highlight the utility of these types of studies for elucidating mechanisms of MDR.

PubMed: 27505298
DOI: 10.1021/acs.biochem.6b00651

Experimental method

X-RAY DIFFRACTION (2.101 Å)