A novel ligand-binding domain involved in regulation of amino acid metabolism in prokaryotes.
A combination of sequence profile searching and structural protein analysis has revealed a novel type of small molecule binding domain that is involved in the allosteric regulation of prokaryotic amino acid metabolism. This domain, designated RAM, has been found to be fused to the DNA-binding domain of Lrp-like transcription regulators and to the catalytic domain of some metabolic enzymes, and has been found as a stand-alone module. Structural analysis of the RAM domain of Lrp reveals a betaalphabetabetaalphabeta-fold that is strikingly similar to that of the recently described ACT domain, a ubiquitous allosteric regulatory domain of many metabolic enzymes. However, structural alignment and re-evaluation of previous mutagenesis data suggest that the effector-binding sites of both modules are significantly different. By assuming that the RAM and ACT domains originated from a common ancestor, these observations suggest that their ligand-binding sites have evolved independently. Both domains appear to play analogous roles in controlling key steps in amino acid metabolism at the level of gene expression as well as enzyme activity.
Laboratory of Microbiology, Wageningen University, Hesselink van Suchtelenweg 4, NL-6307 CT Wageningen, The Netherlands. Thijs.Ettema@algemeen.micr.wau.nl
Thijs J G
TJ
Ettema
Arie B
AB
Brinkman
Travis H
TH
Tani
John B
JB
Rafferty
John
J
Van Der Oost
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism*; D019843:Archaeal Proteins / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins; D001665:Binding Sites; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D019077:Helix-Turn-Helix Motifs; D051756:Leucine-Responsive Regulatory Protein; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D020027:Pyrococcus furiosus / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D016944:Sulfolobus / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
D000596:Amino Acids; D019843:Archaeal Proteins; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D008024:Ligands; C499616:LrpA protein, bacteria; D014157:Transcription Factors; D051756:Leucine-Responsive Regulatory Protein