Phosphoribosylaminoimidazole carboxylase/ phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) is a bifunctional enzyme with both 5-aminoimidazole ribonucleotide (AIR) carboxylase and 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide (SAICAR) synthetase activities. PAICS is an important enzyme in de novo purine biosynthesis. It becomes an attractive target for rational anticancer drug design, since rapidly dividing cancer cells rely heavily on the purine de novo pathway for synthesis of adenine and guanine, whereas normal cells favor the salvage pathway. Here, we report the crystal structure of PAICS from Francisella tularensis subsp. tularensis SCHU S4 at 2.00 A resolution. The structure reveals that eight PAICS subunits, each composed of distinct AIRc and SAICARs domains, assemble a compact homooctamer with an octameric-carboxylase core and four symmetric periphery dimers formed by synthetase domains. At the carboxyaminoimidazole ribonucleotide active site phosphate and formate ions were found. Furthermore, two fructose-6-phosphates were located at the central channel of the octameric protein structure. The structure provides structural information for designing PAICS-specific inhibitors for use in cancer chemotherapy.