Inositol monophosphatase is cleaved by endoprotease lys-C at a single site (Lys36—Ser37). The rate of proteolysis is greatly reduced in the presence of substrate (D,L-Ins(I)P) and Mg2+, and less so in the presence of Pi and Mg2+, consistent with protection of the susceptible bond in the E—P or E·Pi states of the enzyme. Potentiation by Li+ of the protection afforded by a substrate analogue, 1S-phosphoryloxy-2R,4S-dihydroxycyclohexane, and Mg2+ supports the idea that Li+ binds to the E—P state.