Publications

• The stm4066 gene product of Salmonella enterica serovar Typhimurium has aminoimidazole riboside (AIRs) kinase activity and allows AIRs to satisfy the thiamine requirement of pur mutant strains.

  Dougherty M., Downs D.M.

  In bacteria the biosynthetic pathways for purine mononucleotides and the hydroxymethyl pyrimidine moiety of thiamine share five reactions that result in the formation of aminoimidazole ribotide, the last metabolite common to both pathways. Here we describe the characterization of a Salmonella ente ... >> More

  In bacteria the biosynthetic pathways for purine mononucleotides and the hydroxymethyl pyrimidine moiety of thiamine share five reactions that result in the formation of aminoimidazole ribotide, the last metabolite common to both pathways. Here we describe the characterization of a Salmonella enterica mutant strain that has gained the ability to efficiently use exogenous aminoimidazole riboside (AIRs) as a source of thiamine. The lesion responsible for this phenotype is a null mutation in a transcriptional regulator of the GntR family (encoded by stm4068). Lack of this protein derepressed transcription of an associated operon (stm4065-4067) that encoded a predicted kinase. The stm4066 gene product was purified and shown to have AIRs kinase activity in vitro. This activity was consistent with the model presented to explain the phenotype caused by the original mutation. This mutation provides a genetic means to isolate the synthesis of the hydroxymethyl pyrimidine moiety of thiamine from the pathway for purine mononucleotide biosynthesis and thus facilitate in vivo analyses. << Less

  J. Bacteriol. 185:332-339(2003) [PubMed] [EuropePMC]

• Crystal structure of an aminoimidazole riboside kinase from Salmonella enterica: implications for the evolution of the ribokinase superfamily.

  Zhang Y., Dougherty M., Downs D.M., Ealick S.E.

  The crystal structures of a Salmonella enterica aminoimidazole riboside (AIRs) kinase, its complex with the substrate AIRs, and its complex with AIRs and an ATP analog were determined at 2.6 angstroms, 2.9 angstroms, and 2.7 angstroms, respectively. The product of the Salmonella-specific gene stm4 ... >> More

  The crystal structures of a Salmonella enterica aminoimidazole riboside (AIRs) kinase, its complex with the substrate AIRs, and its complex with AIRs and an ATP analog were determined at 2.6 angstroms, 2.9 angstroms, and 2.7 angstroms, respectively. The product of the Salmonella-specific gene stm4066, AIRs kinase, is a homodimer with one active site per monomer. The core structure, consisting of an eight-stranded beta sheet flanked by eight alpha helices, indicates that AIRs kinase is a member of the ribokinase superfamily. Unlike ribokinase and adenosine kinase in this superfamily, AIRs kinase does not show significant conformational changes upon substrate binding. The active site is covered by a lid formed by residues 16-28 and 86-100. A comparison of the structure of AIRs kinase with other ribokinase superfamily members suggests that the active site lid and conformational changes that occur upon substrate binding may be advanced features in the evolution of the ribokinase superfamily. << Less

  Structure 12:1809-1821(2004) [PubMed] [EuropePMC]