3pm1 | pdb_00003pm1
Structure of QacR E90Q bound to Ethidium
Structural highlights
Function[QACR_STAAM] Transcriptional repressor of qacA. Binds to IR1, an unusually long 28 bp operator, which is located downstream from the qacA promoter and overlaps its transcription start site. QacR is induced from its IR1 site by binding to one of many structurally dissimilar cationic lipophilic compounds, which are also substrates of QacA (By similarity). Publication Abstract from PubMedStructures 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. A single acidic residue can guide binding site selection but does not govern QacR cationic-drug affinity.,Peters KM, Brooks BE, Schumacher MA, Skurray RA, Brennan RG, Brown MH PLoS One. 2011 Jan 17;6(1):e15974. PMID:21264225[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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