Mechanism of substrate recognition and catalysis in a mammalian phosphatidylserine synthase 2

Abstract

Mammalian phosphatidylserine synthase-1 and -2 synthesize phosphatidylserine (PS) by replacing the headgroup of either phosphatidylcholine (PC, PTDSS1) or phosphatidylethanolamine (PE, PTDSS2) with a serine. We determined structures of PTDSS2 from Equus caballus in complex with either PE or serine substrates to resolutions of 2.8-3.2 [A]. The structures define substrate binding sites and reveal that the phosphate group of PE is coordinated by two Ca2+. In addition, we found that PTDSS2 has significant phospholipase D (PLD) activity in the absence of serine, which was not reported previously, and that Ca2+ is required for the PLD activity. These discoveries enrich our knowledge in the mechanism of mammalian PTDSS.