A. P-loop composition of different lipid phosphatase activity. Two groups of lipid phosphatases can be assigned based on the different amino acid composition of the active site P-loop. Group 1 contains 3 or more basic residues and a conserved K in position two, while Group 2 have 1 or 2 basic residues and none in position 2. B. Effect of mutagenesis of P-loop residues on the catalytic profile. Specific activity (SA) for WT and mutants of MptpB, Lm1800 and LM1 enzyme using different phosphoinositides as substrates. Addition of a second basic residue in the P-loop increases activity towards di-phosphorylated PIs and results in new activity for MptpB towards PI(3,4,5)P3. Error bars indicate SEM.