title: Phenylacetyl coenzyme A is an effector molecule of the TetR family transcriptional repressor PaaR from Thermus thermophilus HB8.
abstract: Phenylacetic acid (PAA) is a common intermediate in the catabolic pathways of several structurally related aromatic compounds. It is converted into phenylacetyl coenzyme A (PA-CoA), which is degraded to general metabolites by a set of enzymes. Within the genome of the extremely thermophilic bacterium Thermus thermophilus HB8, a cluster of genes, including a TetR family transcriptional regulator, may be involved in PAA degradation. The gene product, which we named T. thermophilus PaaR, negatively regulated the expression of the two operons composing the gene cluster in vitro. T. thermophilus PaaR repressed the target gene expression by binding pseudopalindromic sequences, with a consensus sequence of 5'-CNAACGNNCGTTNG-3', surrounding the promoters. PA-CoA is a ligand of PaaR, with a proposed binding stoichiometry of 1:1 protein monomer, and was effective for transcriptional derepression. Thus, PaaR is a functional homolog of PaaX, a GntR transcriptional repressor found in Escherichia coli and Pseudomonas strains. A three-dimensional structure of T. thermophilus PaaR was predicted by homology modeling. In the putative structure, PaaR adopts the typical three-dimensional structure of the TetR family proteins, with 10 α-helices. A positively charged surface at the center of the molecule is similar to the acyl-CoA-binding site of another TetR family transcriptional regulator, T. thermophilus FadR, which is involved in fatty acid degradation. The CoA moiety of PA-CoA may bind to the center of the PaaR molecule, in a manner similar to the binding of the CoA moiety of acyl-CoA to FadR.
authors: RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors: Keiko
authors: K
authors: Sakamoto
authors: Yoshihiro
authors: Y
authors: Agari
authors: Seiki
authors: S
authors: Kuramitsu
authors: Akeo
authors: A
authors: Shinkai
mesh_terms: D000105:Acetyl Coenzyme A / Q000235:genetics / Q000378:metabolism*; D000214:Acyl Coenzyme A / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015374:Biosensing Techniques; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D005810:Multigene Family; D009876:Operon; D010648:Phenylacetates / Q000378:metabolism; D011994:Recombinant Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016963:Thermus thermophilus / Q000201:enzymology / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D010648:Phenylacetates; D011994:Recombinant Proteins; D012097:Repressor Proteins; D000105:Acetyl Coenzyme A; C037816:phenylacetyl-coenzyme A; C025136:phenylacetic acid