Catalytic mechanism of PRPP synthase. Catalytic mechanism of PRPP synthase. (A) Closure of the catalytic flexible loop of T. volcanium PRPP synthase by superimposition of the open and closed structures (PDB codes 3lrt and 3mbi, respectively). Structural elements are colored as described for Fig. 3A. A 17-Å movement of the catalytic flexible loop, consisting of the β10 and β11 strands, results in the closed conformation necessary for catalysis. (B) Close-up view of the binding of substrates at the active site of T. volcanium PRPP synthase, with open and closed catalytic flexible loops. In the open conformation, the triphosphate chain of ATP, modeled here to only ADP, forms a more or less linear arrangement. In the closed conformation, the triphosphate chain, again modeled to only ADP, bends with the β-phosphate, resulting in a position ideal for attack of O-1 of ribose 5-phosphate on the β-phosphorus. An Mg2+ of the closed conformation is shown as a black sphere (138). (C) Stereo view of the binding of ribose 5-phosphate, Mg2+, and the transition state analog AlF3 to the active site of B. subtilis PRPP synthase, AlF3 PRPP synthase. (Reproduced from reference 54 with permission.) α indicates the α-phosphate of ATP provided by an AMP molecule; β indicates the β-phosphate of ATP provided by Al3+ (bound to three F− ions); γ indicates the γ-phosphate of ATP provided by the phosphate of a second AMP molecule. The two Mg2+ are indicated by MG1 and MG2. Relevant amino acid residues His135, Asp174, Lys197, and Arg199 are included as well. (D) Stereo view of the binding of ribose 5-phosphate, α,β-methylene ATP, Mg2+, and Ca2+ to the active site of B. subtilis PRPP synthase in the GDP PRPP synthase complex. (Reproduced from reference 54 with permission.) Ca2+ (designated CA1) coordinates to the hydroxyls at C-1, C-2, and C-3 of ribose 5-phosphate, oxygen of the β- and γ-phosphates of α,β-methylene ATP, Asp174, as well as a water molecule. The Mg2+ (designated MG2) coordinates to the oxygen of C-2′ of the ribosyl moiety as well as oxygen of the α- and γ-phosphates of α,β-methylene ATP, as well as to three water molecules. Thus, there is no coordination to oxygen of the β-phosphate of α,β-methylene ATP. Bjarne Hove-Jensen et al. Microbiol. Mol. Biol. Rev. 2017; doi:10.1128/MMBR.00040-16