Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB359 in multiple positions.

Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB359 in multiple positions. Research Abstract Details 

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Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB359 in multiple positions. Abstract Text:

Benjamin E Brooks,Kevin M Piro,Richard G Brennan,

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.

Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB359 in multiple positions. Publishing Authors By Initials

BE Brooks,KM Piro,RG Brennan,

For similar proteins: transcription factors: repressor proteins research abstracts see: proteins: transcription factors: repressor proteins research

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Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB359 in multiple positions. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of the American Chemical Society

VOLUME: 129

Page Numbers: 8389-95

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 13

MONTH: 06

YEAR: 2007

Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB359 in multiple positions. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB359 in multiple positions. Keywords Mesh Terms:

KEYWORDS: Repressor Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB359 in multiple positions. Information

Substance Name: furamidine

Registry Number: 73819-26-8

Grant and Affiliation Information for Multidrug-binding transcription factor QacR binds the bivalent aromatic diamidines DB75 and DB359 in multiple positions.

AFFILIATION: Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Unit 1000, Houston, TX 77030, USA.

Country: United States

AGENCY: United States NIAID

GRANT: AI48593

ACRONYM: AI

MEDLINETA: J Am Chem Soc

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