Cloning and crystal structure of hematopoietic prostaglandin D synthase
Cloning and crystal structure of hematopoietic prostaglandin D synthase
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DOI：
10.1016/s0092-8674(00)80374-8
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发表时间：
1997-09-19
期刊：
影响因子：
64.5
通讯作者：
Hayaishi, O
中科院分区：
文献类型：
--
作者：
Kanaoka, Y;Ago, H;Hayaishi, O
造血前列腺素 (PG) D 合酶是免疫系统和肥大细胞中产生 D 和 J 系列前列腺素的关键酶。我们分离了大鼠酶的 cDNA，使重组酶结晶，并以 2.3 埃的分辨率测定了与谷胱甘肽复合的酶的三维结构。该酶是来自脊椎动物的 sigma 类谷胱甘肽 S-转移酶 (GST) 的第一个成员，并具有一个突出的裂缝作为活性位点，这在 GST 家族的其他成员中从未见过。裂口独特的 3-D 结构导致了假定的底物结合及其催化机制，负责从 PGH(2) 到 PGD(2) 的特异性异构化。
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 Angstrom 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 made and its catalytic mechanism, responsible for the specific isomerization from PGH(2) to PGD(2).