3PM1

Structure of QacR E90Q bound to Ethidium

Summary for 3PM1

• Entry DOI: 10.2210/pdb3pm1/pdb
• Related: 1JT6 1JTY 1JUP 1JUS 3BQZ 3BR0 3BR1 3BR2 3BR4 3BR5 3BR6
• Descriptor: HTH-type transcriptional regulator qacR, SULFATE ION, ETHIDIUM, ... (4 entities in total)
• Functional Keywords: tetr family member, transcription regulation, multidrug resistance, dna, nucleoid, transcription
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 46866.72

Authors

Schumacher, M.A. (deposition date: 2010-11-15, release date: 2011-07-13, Last modification date: 2024-04-03)

Primary citation

Peters, K.M.,Brooks, B.E.,Schumacher, M.A.,Skurray, R.A.,Brennan, R.G.,Brown, M.H.
A single acidic residue can guide binding site selection but does not govern QacR cationic-drug affinity.
Plos One, 6:e15974-e15974, 2011

PubMed Abstract: Structures of the multidrug-binding repressor protein QacR with monovalent and bivalent cationic drugs revealed that the carboxylate side-chains of E90 and E120 were proximal to the positively charged nitrogens of the ligands ethidium, malachite green and rhodamine 6G, and therefore may contribute to drug neutralization and binding affinity. Here, we report structural, biochemical and in vivo effects of substituting these glutamate residues. Unexpectedly, substitutions had little impact on ligand affinity or in vivo induction capabilities. Structures of QacR(E90Q) and QacR(E120Q) with ethidium or malachite green took similar global conformations that differed significantly from all previously described QacR-drug complexes but still prohibited binding to cognate DNA. Strikingly, the QacR(E90Q)-rhodamine 6G complex revealed two mutually exclusive rhodamine 6G binding sites. Despite multiple structural changes, all drug binding was essentially isoenergetic. Thus, these data strongly suggest that rather than contributing significantly to ligand binding affinity, the role of acidic residues lining the QacR multidrug-binding pocket is primarily to attract and guide cationic drugs to the "best available" positions within the pocket that elicit QacR induction.

PubMed: 21264225
DOI: 10.1371/journal.pone.0015974

Experimental method

X-RAY DIFFRACTION (2.8 Å)