2HQ5
Crystal structure of multidrug binding protein QacR from Staphylococcus aureus cocrystallized with compound DB359
Summary for 2HQ5
| Entry DOI | 10.2210/pdb2hq5/pdb |
| Related | 1JT6 1RKW 1RPW 2DTZ |
| Descriptor | HTH-type transcriptional regulator qacR, SULFATE ION (3 entities in total) |
| Functional Keywords | multidrug recognition, db359, qacr, multidrug binding protein, transcription |
| Biological source | Staphylococcus aureus |
| Total number of polymer chains | 4 |
| Total formula weight | 93276.97 |
| Authors | Brooks, B.E.,Brennan, R.G. (deposition date: 2006-07-18, release date: 2007-07-17, Last modification date: 2023-10-25) |
| Primary citation | Brooks, B.E.,Piro, K.M.,Brennan, R.G. Multidrug-Binding Transcription Factor QacR Binds the Bivalent Aromatic Diamidines DB75 and DB359 in Multiple Positions J.Am.Chem.Soc., 129:8389-8395, 2007 Cited by PubMed Abstract: Staphylococcus aureus QacR is a multidrug-binding transcription repressor. Crystal structures of multiple QacR-drug complexes reveal that these toxins bind in a large pocket, which is composed of smaller overlapping "minipockets". Stacking, van der Waals, and ionic interactions are common features of binding, whereas hydrogen bonds are limited. Pentamidine, a bivalent aromatic diamidine, interacts with QacR differently as one positively charged benzamidine moiety is neutralized by the dipoles of side-chain and peptide backbone oxygens rather than a formal negative charge from proximal acidic residues. To understand the binding mechanisms of other bivalent benzamidines, we determined the crystal structures of the QacR-DB75 and QacR-DB359 complexes and measured their binding affinities. Although these rigid aromatic diamidines bind with low-micromolar affinities, they do not use single, discrete binding modes. Such promiscuous binding underscores the intrinsic chemical redundancy of the QacR multidrug-binding pocket. Chemical redundancy is likely a hallmark of all multidrug-binding pockets, yet it is utilized by only a subset of drugs, which, for QacR, so far appears to be limited to chemically rigid, bivalent compounds. PubMed: 17567017DOI: 10.1021/ja072576v PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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