Purification, characterization and mode of action of PdhR, the transcriptional repressor of the pdhR-aceEF-lpd operon of Escherichia coli

Mol Microbiol. 1995 Feb;15(3):519-29. doi: 10.1111/j.1365-2958.1995.tb02265.x.

Abstract

The repressor of the pdhR-aceEF-lpd operon of Escherichia coli, PdhR, was amplified to 23% of total cell protein and purified to homogeneity by heparin-agarose and cation-exchange chromatography. The purified protein is a monomer (M(r) 29,300) which binds specifically to DNA fragments containing the pdh promoter (Ppdh) in the absence of pyruvate. The pdh operator was identified by DNase I footprinting as a region of hyphenated dyad symmetry, +11AATTGGTaagACCAATT+27, situated just downstream of the transcript start site. In vitro transcription from Ppdh was repressed > 1000-fold by PdhR and this repression was antagonized in a concentration-dependent manner by its co-effector, pyruvate. Studies on RNA polymerase binding at Ppdh showed that RNA polymerase protects the -44 to +21 region in the absence of PdhR, but no RNA polymerase binding or protection upstream of +9 could be detected in the presence of PdhR. It is concluded that PdhR represses transcription by binding to an operator site centred at +19 such that effective binding of RNA polymerase is prevented.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / biosynthesis
  • Acetyltransferases / genetics*
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / isolation & purification*
  • Base Sequence
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism
  • DNA-Directed RNA Polymerases / metabolism
  • Dihydrolipoamide Dehydrogenase / biosynthesis
  • Dihydrolipoamide Dehydrogenase / genetics*
  • Dihydrolipoyllysine-Residue Acetyltransferase
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins*
  • Gene Expression Regulation, Bacterial* / drug effects
  • Ketoglutarate Dehydrogenase Complex / biosynthesis
  • Ketoglutarate Dehydrogenase Complex / genetics*
  • Molecular Sequence Data
  • Operon / genetics
  • Pyruvate Dehydrogenase Complex / biosynthesis
  • Pyruvate Dehydrogenase Complex / genetics*
  • Pyruvates
  • Pyruvic Acid
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / isolation & purification*
  • Transcription Factors / genetics
  • Transcription Factors / isolation & purification*

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • Escherichia coli Proteins
  • PdhR protein, E coli
  • Pyruvate Dehydrogenase Complex
  • Pyruvates
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Transcription Factors
  • Pyruvic Acid
  • Ketoglutarate Dehydrogenase Complex
  • lpd protein, E coli
  • Dihydrolipoamide Dehydrogenase
  • Acetyltransferases
  • Dihydrolipoyllysine-Residue Acetyltransferase
  • DNA-Directed RNA Polymerases