Steve Ealick's Research Group
Salmonella enterica Aminoimidazole Riboside Kinase
1TYY: unliganded AIRs kinase
1TZ3: AIRs kinase/AIRs complex
1TZ6: AIRs kinase/AIRs/AMP-PCP complex
In the biosynthetic pathways of purines and thiamin in bacteria, 5-aminoimidazole ribotide (AIR) serves as a branch point metabolite. AIR is then either converted to carboxyaminoimidazole ribotide, the next intermediate in purine biosynthesis, or 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMPP), the pyrimidine moiety of thiamin. Biosynthesis of AIR requires five enzymatic steps.Although AIR cannot be efficiently taken up by most bacteria, it can be salvaged by the phosphorylation of aminoimidazole riboside (AIRs). In Salmonella enterica the overexpression of gene stm4066 facilitatedAIRs salvage, and it was determined that stm4066 gene product has aminoimidazole riboside kinase activity.
The core structure of the monomer indicates that AIRs kinase may be a member of the ribokinase superfamily as are 4-methyl-5-b-hydroxyethylthiazole kinase (THZ kinase or ThiK) and 4-Amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase (HMPP kinase or ThiD) for which we determined the structures.
|AIRs kinase is an elongated homodimer that shows some asymmetry, because the monomers differ slightly in the "lid" regions.|
|Each AIRs kinase monomer has one active site, located along one edge of the central β-sheet, with the AIRs binding site at near the lid and the ATP binding site at the other end. The schematic at right shows the active site, with key hydrogen bonding residues indicated by dashed lines.|
Zhang Y, Dougherty M, Downs DM and Ealick SE. Crystal Structure of an aminoimidazole riboside kinase from Salmonella enterica: Implications for the evolution of the ribokinase superfamily of proteins, Structure 12:1809-1821 (2004).