Mechanism Sphingomyelin phosphodiesterase

the solving of crystal structure of neutral sphingomyelinase listeria ivanovii , bacillus cereus has shed light on catalytic mechanisms. active site of smase contains glu , residues each bound 1 or 2 divalent metal cations, co, mg, or ca optimum performance. these 2 cations assist in catalysis recruiting sm active site of smase. divalent cation bound glu residue interacts amido-oxygen , ester-oxygen between c1 , phosphate group of sm; asn residue , divalent metal cation bound residue bind oxygen atoms of phosphate group of sm. stabilizes phosphate group’s negative charge. metal cation bound residue , asp , asn side chains lower pka value of 1 of bridged water molecules, activating water molecule. water molecule acts nucleophile , attacks phosphate group of sm, creating pentavalent phosphorus atom negative charge stabilized divalent metal cations. phosphate reforms tetrahedral conformation , results in products ceramide , phosphocholine. however, not clear if mechanism of action of acidic sphingomyelinase same, owing lack of crystal structure.