Mechanisms of substrate recognition and catalysis in a mammalian phosphatidylserine synthase 2.

Mammalian phosphatidylserine synthase-1 and -2, PSS1 and PSS2, synthesize phosphatidylserine (PS) by replacing the headgroup of either phosphatidylcholine or phosphatidylethanolamine (PE) with a serine. We determined structures of PSS2 from Equus caballus in complex with either a PE or a serine substrate to resolutions of 2.8 to 3.2 Å. The structures define substrate binding sites and reveal that the phosphate group of the PE is coordinated by two Ca2+. In addition, we found that PSS2 has significant phospholipase D (PLD) activity in the absence of serine and that Ca2+ is required for the PLD activity. These findings enrich and refine our knowledge in the mechanisms of substrate recognition and catalysis in mammalian PSS.