5.4.99.18 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole = 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate - - 5.4.99.18 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole = 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate common, buried carboxylate or CO2 binding site for substrate and product in a hydrophobic pocket, in which the carboxylate or CO2 interacts with backbone amides. The carboxylate orients the substrate for proton transfer from His45 to 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole to form an enzyme-bound aminoimidazole ribonucleotide and CO2 intermediate. subsequent movement of the aminoimidazole moiety reorients it for addition of CO2 at C4 to generate iso-5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate. H5 is now in a position to remove a C4 proton to produce 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate 678260 5.4.99.18 5-carboxyamino-1-(5-phospho-D-ribosyl)imidazole = 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate H89 is not essential and does not function as part of a proton relay system. For synthesis of 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate, the carboxylate moiety is positioned in a small pocket proposed to facilitate nucleotide decarboxylation. In the reverse direction, enzyme favors protonation of 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate C4 678203