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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites / physiology
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Cloning, Molecular
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Crystallography
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DNA, Complementary
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Epoprostenol / metabolism
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Gene Expression Regulation, Enzymologic
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Hematopoiesis / physiology
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Intramolecular Oxidoreductases*
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Isomerases / chemistry*
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Isomerases / genetics*
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Isomerases / metabolism
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Isomerism
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Lipocalins
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Molecular Sequence Data
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Prostaglandin D2 / chemistry
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Prostaglandin D2 / metabolism
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Prostaglandin H2
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Prostaglandins H / chemistry
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Prostaglandins H / metabolism
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Protein Structure, Tertiary
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Sequence Homology, Amino Acid
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Substrate Specificity
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Thromboxane A2 / metabolism
Substances
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DNA, Complementary
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Lipocalins
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Prostaglandins H
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RNA, Messenger
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Prostaglandin H2
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Thromboxane A2
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Epoprostenol
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Isomerases
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Intramolecular Oxidoreductases
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prostaglandin R2 D-isomerase
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Prostaglandin D2