Thioredoxin reductase two modes of catalysis have evolved.
Thioredoxin reductase two modes of catalysis have evolved.
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DOI：
10.1046/j.1432-1327.2000.01702.x
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发表时间：
2000-10
期刊：
影响因子：
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通讯作者：
C. Williams;L. Arscott;S. Müller;B. Lennon;M. Ludwig;Pan‐Fen Wang;D. M. Veine;K. Becker;R. Schirmer
中科院分区：
文献类型：
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作者：
C. Williams;L. Arscott;S. Müller;B. Lennon;M. Ludwig;Pan‐Fen Wang;D. M. Veine;K. Becker;R. Schirmer
硫氧还蛋白还原酶（EC 1.6.4.5）是广泛分布的黄素蛋白，其催化硫氧还蛋白的NADPH依赖性还原。硫氧还蛋白在维持细胞的氧化还原环境中起着几个关键作用。与硫辛酰胺脱氢酶、谷胱甘肽还原酶和汞还原酶等酶家族的所有成员一样，硫氧还蛋白还原酶含有一个与黄素环相邻的氧化还原活性二硫化物。进化产生了两种形式的硫氧还蛋白还原酶，一种是原核生物、古生菌和低等真核生物中的蛋白质，其Mr为35000，另一种是高等真核生物中的蛋白质，其Mr为55000。还原当量从非极性黄素结合位点转移到蛋白质底物的两种形式的硫氧还蛋白还原酶的不同机制。在低Mr酶中，两种构象之间的相互转化在每个催化循环中发生两次。在二硫化物被黄素还原后，吡啶核苷酸结构域必须相对于黄素结构域旋转，以暴露新生的二硫醇与硫氧还蛋白反应;这种运动将吡啶环重新定位在黄素环附近。在高Mr酶中，第三个氧化还原活性基团将还原当量从非极性活性位点穿梭到蛋白质表面。该基团是恶性疟原虫硫氧还蛋白还原酶中的第二氧化还原活性二硫化物和哺乳动物酶中的硒基硫化物。恶性疟原虫是疟疾的主要病原体，人们希望这两种高Mr形式之间的化学差异可以用于药物设计。
Thioredoxin reductase (EC 1.6.4.5) is a widely distributed flavoprotein that catalyzes the NADPH-dependent reduction of thioredoxin. Thioredoxin plays several key roles in maintaining the redox environment of the cell. Like all members of the enzyme family that includes lipoamide dehydrogenase, glutathione reductase and mercuric reductase, thioredoxin reductase contains a redox active disulfide adjacent to the flavin ring. Evolution has produced two forms of thioredoxin reductase, a protein in prokaryotes, archaea and lower eukaryotes having a Mr of 35 000, and a protein in higher eukaryotes having a Mr of 55 000. Reducing equivalents are transferred from the apolar flavin binding site to the protein substrate by distinct mechanisms in the two forms of thioredoxin reductase. In the low Mr enzyme, interconversion between two conformations occurs twice in each catalytic cycle. After reduction of the disulfide by the flavin, the pyridine nucleotide domain must rotate with respect to the flavin domain in order to expose the nascent dithiol for reaction with thioredoxin; this motion repositions the pyridine ring adjacent to the flavin ring. In the high Mr enzyme, a third redox active group shuttles the reducing equivalent from the apolar active site to the protein surface. This group is a second redox active disulfide in thioredoxin reductase from Plasmodium falciparum and a selenenylsulfide in the mammalian enzyme. P. falciparum is the major causative agent of malaria and it is hoped that the chemical difference between the two high Mr forms may be exploited for drug design.