2DTZ: Crystal Structure Of Multidrug Binding Protein Qacr From Staphylococcus Aureus Cocrystallized With Compound Db75

Citation:
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.
PDB ID: 2DTZDownload
MMDB ID: 47353
PDB Deposition Date: 2006/7/19
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 2DTZ: dimeric; determined by author and by software (PISA)
Molecular Components in 2DTZ
Label Count Molecule
Proteins (2 molecules)
2
Hth-type Transcriptional Regulator Qacr(Gene symbol: qacR)
Molecule annotation
Chemicals (3 molecules)
1
3
* Click molecule labels to explore molecular sequence information.

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