page_title: Phosphatidate phosphatase
section_title: Type II
hierarchical_section_title: Phosphatidate phosphatase / Types / Type II
caption_attribution_description: English: Dephosphorylation of phosphatidylglycerol phosphate (PGP) to form PG (phosphatidylglycerol). This reaction is catalyzed by PgpB, a bacterial integral membrane lipid phosphate phosphatase.
context_page_description: Phosphatidate phosphatase is a key regulatory enzyme in lipid metabolism, catalyzing the conversion of phosphatidate to diacylglycerol. The two substrates of PAP are phosphatidate and H₂O, and its two products are diacylglycerol and phosphate, as shown here.
  a 1,2-diacylglycerol 3-phosphate + H₂O a 1,2-diacyl-sn-glycerol + phosphate
  The reverse reaction is catalyzed by the enzyme diacylglycerol kinase, which replaces the hydroxyl group on diacylgylcerol with a phosphate from ATP, generating ADP in the process. While ATP is used by DGK in mammalian cells, yeast cells tend to use CTP as the high-energy phosphate donor instead. Mechanistically speaking, this has no effect on the overall reaction.
  In yeast, the forward direction is -dependent, while the reverse direction is -dependent. PAP1, a cytosolic phosphatidate phosphatase found in the lung, is also -dependent, but PAP2, a six-transmembrane-domain integral protein found in the plasma membrane, is not.
context_section_description: Type II phosphatidate phosphatases are transmembrane enzymes found mainly in the plasma membrane. They can dephosphorylate other substrates besides phosphatidate, and therefore are also known as lipid phosphate phosphatases.  Their main role is in lipid signaling and in phospholipid head-group remodeling.
  One example of a type II phosphatidate phosphatase is PgpB (PDBe: 5jwy). PgpB is one of three integral membrane phosphatases in Escherichia coli that catalyzes the dephosphorylation of phosphatidylglycerol phosphate (PGP) to PG (phosphatidylglycerol). The other two are PgpA and PgpC. While all three catalyze the reaction from PGP to PG, their amino acid sequences are dissimilar and it is predicted that their active sites open to different sides of the cytoplasmic membrane. PG accounts for approximately 20% of the total membrane lipid composition in the inner membrane of bacteria. PgpB is competitively inhibited by phosphatidylethanolamine (PE), a phospholipid formed from DAG. This is therefore an example of negative feedback regulation. The enzyme active site contains a catalytic triad Asp-211, His-207, and His-163 that establishes a charge relay system. However, this catalytic triad is essential for the dephosphorylation of lysophosphatidic acid, phosphatidic acid, and sphingosine-1-phosphate, but is not essential in its entirety for the enzyme's native substrate, phosphatidylglycerol phosphate; His-207 alone is sufficient to hydrolyze PGP.
  In the cartoon depiction of PgpB below, one can see its six transmembrane alpha helices, which are here shown horizontally. Of the three PGP phosphatases discussed above, PgpB is the only to have multiple transmembrane alpha helices.
caption: Dephosphorylation of phosphatidylglycerol phosphate (PGP) to form PG (phosphatidylglycerol). This reaction is catalyzed by PgpB, a bacterial integral membrane lipid phosphate phosphatase.
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