Structural basis for CO2 fixation by a novel member of the disulfide oxidoreductase family of enzymes, 2-ketopropyl-coenzyme M oxidoreductase/carboxylase
Structural basis for CO2 fixation by a novel member of the disulfide oxidoreductase family of enzymes, 2-ketopropyl-coenzyme M oxidoreductase/carboxylase
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DOI：
10.1021/bi026580p
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发表时间：
2002-10-29
期刊：
影响因子：
2.9
通讯作者：
Peters, JW
中科院分区：
文献类型：
--
作者：
Nocek, B;Jang, SB;Peters, JW
NADPH：2-酮丙基-辅酶M氧化还原酶/羧化酶（2-KPCC）是导致自营黄杆菌Py 2中丙烯转化为中心代谢物乙酰乙酸的代谢途径中的末端酶。这种酶是一种含FAD的酶，是NADPH：二硫键氧化还原酶（DSOR）家族的成员，包括谷胱甘肽还原酶、二氢硫辛酰胺脱氢酶、锥虫硫酮还原酶、硫氧还蛋白还原酶和汞还原酶。与DSOR家族成员催化的原型反应相反，NADPH：2-酮丙基-辅酶M氧化还原酶/羧化酶催化2-酮丙基-辅酶M的硫醚键的还原裂解，以及随后酮丙基裂解产物的羧化，产生产物乙酰乙酸酯和游离辅酶M。2-KPCC的结构揭示了与DSOR酶家族的其他成员相比独特的活性位点，并展示了酶结构如何适应更复杂的生化反应。此外，在天然状态下的结构和在结合底物的存在下的结构的比较表明，底物2-酮丙基-辅酶M的结合诱导构象变化，导致底物进入通道的塌陷。以这种方式包裹底物让人想起在充分表征的CO2固定酶核酮糖1，5-二磷酸羧化酶/氧化酶（Rubisco）中观察到的构象变化。
The NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC) is the terminal enzyme in a metabolic pathway that results in the conversion of propylene to the central metabolite acetoacetate in Xanthobacter autotrophicus Py2. This enzyme is an FAD-containing enzyme that is a member of the NADPH:disulfide oxidoreductase (DSOR) family of enzymes that include glutathione reductase, dihydrolipoamide dehydrogenase, trypanothione reductase, thioredoxin reductase, and mercuric reductase. In contrast to the prototypical reactions catalyzed by members of the DSOR family, the NADPH: 2-ketopropyl-coenzyme M oxidoreductase/carboxylase catalyzes the reductive cleavage of the thioether linkage of 2-ketopropyl-coenzyme M, and the subsequent carboxylation of the ketopropyl cleavage product, yielding the products acetoacetate and free coenzyme M. The structure of 2-KPCC reveals a unique active site in comparison to those of other members of the DSOR family of enzymes and demonstrates how the enzyme architecture has been adapted for the more sophisticated biochemical reaction. In addition, comparison of the structures in the native state and in the presence of bound substrate indicates the binding of the substrate 2-ketopropyl-coenzyme M induces a conformational change resulting in the collapse of the substrate access channel. The encapsulation of the substrate in this manner is reminiscent of the conformational changes observed in the well-characterized CO2-fixing enzyme ribulose 1,5-bisphosphate carboxylase/oxidase (Rubisco).