In enzymology, a phosphoribosyl-ATP diphosphatase (EC 3.6.1.31) is an enzyme that catalyzes the chemical reaction

1-(5-phosphoribosyl)-ATP + H₂O 1-(5-phosphoribosyl)-AMP + diphosphate

Thus, the two substrates of this enzyme are 1-(5-phosphoribosyl)-ATP and H₂O, whereas its two products are 1-(5-phosphoribosyl)-AMP and diphosphate.

This enzyme participates in histidine metabolism. It employs one cofactor, H+.

This enzyme belongs to the family of hydrolases, specifically those acting on acid anhydrides in phosphorus-containing anhydrides. The systematic name of this enzyme class is 1-(5-phosphoribosyl)-ATP diphosphohydrolase. Other names in common use include phosphoribosyl-ATP pyrophosphatase, and phosphoribosyladenosine triphosphate pyrophosphatase.

• Smith DW, Ames BN (July 1965). "Phosphoribosyladenosine monophosphate, an intermediate in histidine biosynthesis". The Journal of Biological Chemistry. 240 (7): 3056–63. doi:10.1016/S0021-9258(18)97286-8. PMID 14342333.