title: Cloning and crystal structure of hematopoietic prostaglandin D synthase.
abstract: Hematopoietic prostaglandin (PG) D synthase is the key enzyme for production of the D and J series of prostanoids in the immune system and mast cells. We isolated a cDNA for the rat enzyme, crystallized the recombinant enzyme, and determined the three-dimensional structure of the enzyme complexed with glutathione at 2.3 A resolution. The enzyme is the first member of the sigma class glutathione S-transferase (GST) from vertebrates and possesses a prominent cleft as the active site, which is never seen among other members of the GST family. The unique 3-D architecture of the cleft leads to the putative substrate binding mode and its catalytic mechanism, responsible for the specific isomerization from PGH2 to PGD2.
authors.affiliation: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kanaoka
authors.forename: H
authors.initials: H
authors.lastname: Ago
authors.forename: E
authors.initials: E
authors.lastname: Inagaki
authors.forename: T
authors.initials: T
authors.lastname: Nanayama
authors.forename: M
authors.initials: M
authors.lastname: Miyano
authors.forename: R
authors.initials: R
authors.lastname: Kikuno
authors.forename: Y
authors.initials: Y
authors.lastname: Fujii
authors.forename: N
authors.initials: N
authors.lastname: Eguchi
authors.forename: H
authors.initials: H
authors.lastname: Toh
authors.forename: Y
authors.initials: Y
authors.lastname: Urade
authors.forename: O
authors.initials: O
authors.lastname: Hayaishi
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D003001:Cloning, Molecular; D003461:Crystallography; D018076:DNA, Complementary; D011464:Epoprostenol / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006410:Hematopoiesis / Q000502:physiology; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D007536:Isomerism; D054834:Lipocalins; D008969:Molecular Sequence Data; D015230:Prostaglandin D2 / Q000737:chemistry / Q000378:metabolism; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D054834:Lipocalins; D011463:Prostaglandins H; D012333:RNA, Messenger; D044262:Prostaglandin H2; D013928:Thromboxane A2; D011464:Epoprostenol; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2