We report the crystal structures of human hematopoietic prostaglandin (PG) D synthase bound to glutathione (GSH) and Ca
2+ or Mg
2+. Using GSH as a cofactor, prostaglandin D synthase catalyzes the isomerization of PGH
2 to PGD
2, a mediator for allergy response. The enzyme is a homodimer, and Ca
2+ or Mg
2+ increases its activity to - 150 % of the basal level, with half maximum effective concentrations of 400 μM for Ca
2+ and 50 μM for Mg
2+. In the Mg
2+-bound form, the ion is octahedrally coordinated by six water molecules at the dimer interface. The water molecules are surrounded by pairs of Asp93, Asp96 and Asp97 from each subunit. Ca
2+ is coordinated by five water molecules and an Asp96 from one subunit. The Asp96 residue in the Ca
2+-bound form makes hydrogen bonds with two guanidium nitrogen atoms of Arg 14 in the GSH-binding pocket. Mg
2+ alters the coordinating water structure and reduces one hydrogen bond between Asp96 and Arg14, thereby changing the interaction between Arg 14 and GSH. This effect explains a four-fold reduction in the
Km of the enzyme for GSH. The structure provides insights into how Ca
2+ or Mg
2+ binding activates human hematopoietic PGD Synthase.
抄録全体を表示