The purine repressor of Bacillus subtilis: A novel combination of domains adapted for transcription regulation

Sangita C. Sinha, Joseph Krahn, Byung Sik Shin, Diana R. Tomchick, Howard Zalkin, Janet L. Smith

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The purine repressor from Bacillus subtilis, PurR, represses transcription from a number of genes with functions in the synthesis, transport, and metabolism of purines. The 2.2-Å crystal structure of PurR reveals a two-domain protein organized as a dimer. The larger C-terminal domain belongs to the PRT structural family, in accord with a sequence motif for binding the inducer phosphoribosylpyrophosphate (PRPP). The PRT domain is fused to a smaller N-terminal domain that belongs to the winged-helix family of DNA binding proteins. A positively charged surface on the winged-helix domain likely binds specific DNA sequences in the recognition site. A second positively charged surface surrounds the PRPP site at the opposite end of the PurR dimer. Conserved amino acids in the sequences of PurR homologs in 21 gram-positive bacteria cluster on the proposed recognition surface of the winged-helix domain and around the PRPP binding site at the opposite end of the molecule, supporting a common function of DNA and PRPP binding for all of the proteins. The structure supports a binding mechanism in which extended regions of DNA interact with extensive protein surface. Unlike most PRT proteins, which are phosphoribosyltransferases (PRTases), PurR lacks catalytic activity. This is explained by a tyrosine side chain that blocks the site for a nucleophile cosubstrate in PRTases. Thus, B. subtilis has adapted an enzyme fold to serve as an effector-binding domain and has used it in a novel combination with the DNA-binding winged-helix domain as a repressor of purine genes.

Original languageEnglish (US)
Pages (from-to)4087-4098
Number of pages12
JournalJournal of bacteriology
Volume185
Issue number14
DOIs
StatePublished - Jul 2003

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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