CLONING AND CRYSTAL-STRUCTURE OF HEMATOPOIETIC PROSTAGLANDIN-D SYNTHASE

Hematopoietic prostaglandin (PG) D synthase is the key enzyme for prod uction of the D and J series of prostanoids in the immune system and m ast cells. We isolated a cDNA for the rat enzyme, crystallized the rec ombinant enzyme, and determined the three-dimensional structure of the enzyme complexed with glutathione at 2.3 Angstrom resolution. The enz yme is the first member of the sigma class glutathione S-transferase ( GST) from vertebrates and possesses a prominent cleft as the active si te, which is never seen among other members of the GST family. The uni que 3-D architecture of the cleft leads to the putative substrate bind ing made and its catalytic mechanism, responsible for the specific iso merization from PGH(2) to PGD(2).