2hq5
From Proteopedia
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Crystal structure of multidrug binding protein QacR from Staphylococcus aureus cocrystallized with compound DB359
Overview
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.
About this Structure
2HQ5 is a Single protein structure of sequence from Staphylococcus aureus with as ligand. Full crystallographic information is available from OCA.
Reference
Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB359 in multiple positions., Brooks BE, Piro KM, Brennan RG, J Am Chem Soc. 2007 Jul 4;129(26):8389-95. Epub 2007 Jun 13. PMID:17567017
Page seeded by OCA on Thu Feb 21 17:44:33 2008
