title: The purine repressor of Bacillus subtilis: a novel combination of domains adapted for transcription regulation.
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-A 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.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Sangita C
authors.initials: SC
authors.lastname: Sinha
authors.forename: Joseph
authors.initials: J
authors.lastname: Krahn
authors.forename: Byung Sik
authors.initials: BS
authors.lastname: Shin
authors.forename: Diana R
authors.initials: DR
authors.lastname: Tomchick
authors.forename: Howard
authors.initials: H
authors.lastname: Zalkin
authors.forename: Janet L
authors.initials: JL
authors.lastname: Smith
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D015964:Gene Expression Regulation, Bacterial; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012984:Software; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C065825:PurR protein, Bacteria; D012097:Repressor Proteins; D010754:Phosphoribosyl Pyrophosphate; D004247:DNA