Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase - Conservation of the ancestral genomic structure of sigma-class glutathione S-transferase

Hematopoietic prostaglandin D synthase (H-PGDS) is the key enzyme for the p roduction of the D and J series of prostanoids, and the first recognized ve rtebrate homolog of sigma-class glutathione S-transferase (GST). We isolate d the genes and cDNAs for human and mouse H-PGDSs. The human and mouse cDNA s contained a coding region corresponding to 199 amino-acid residues with c alculated molecular masses of 23 343 and 23 226, respectively. Both H-PGDS proteins recombinantly expressed in Escherichia coli showed bifunctional ac tivities for PGDS and GST, and had almost the same catalytic properties as the rat enzyme. Northern analyses demonstrated that the H-PGDS genes were e xpressed in a highly species-specific manner. Whereas the human gene was wi dely distributed, in contrast, the mouse gene was detected only in samples from oviduct and skin. By fluorescence in situ hybridization, the chromosom al localization of the human and mouse H-PGDS genes were mapped to 4q21-22 and 3D-E, respectively. The human and mouse H-PGDS genes spanned approximat ely 41 and 28 kb, respectively, and consisted of six exons divided by five introns. The exon/intron boundaries of both genes were completely identical to those of the sigma-class GST subfamily, although the amino-acid sequenc es of the latter were only 17.0-21.5% identical to those of either H-PGDS. These findings suggest that the H-PGDS genes evolved from the same ancestra l gene as the members of the sigma-class GST family.