Cloning and crystal structure of hematopoietic prostaglandin D synthase.
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.
Kanaoka
Y
Y
Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Japan.
Ago
H
H
Inagaki
E
E
Nanayama
T
T
Miyano
M
M
Kikuno
R
R
Fujii
Y
Y
Eguchi
N
N
Toh
H
H
Urade
Y
Y
Hayaishi
O
O
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
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