NADPH-cytochrome P450 oxidoreductase: prototypic member of the diflavin reductase family.
NADPH-cytochrome P450 oxidoreductase: prototypic member of the diflavin reductase family.
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DOI：
10.1016/j.abb.2012.09.002
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发表时间：
2012-12-01
影响因子：
3.9
通讯作者：
Kim, Jung-Ja P.
中科院分区：
文献类型：
--
作者：
Iyanagi, Takashi;Xia, Chuanwu;Kim, Jung-Ja P.
关键词：
NADPH-细胞色素 P450 氧化还原酶 (CYPOR) 和一氧化氮合酶 (NOS) 是二黄素氧化还原酶家族的两个成员，是包含通过柔性铰链连接的不同 FAD 和 FMN 结构域的多结构域酶。 FAD 接受来自 NADPH 的氢负离子，还原后的 FAD 向 FMN 提供电子，FMN 又将电子转移到细胞色素 P450 或 NOS 加氧酶结构域的血红素中心。 CYPOR（该酶家族的原型）的结构分析揭示了结构域排列的确切性质以及参与辅因子结合的残基的作用。最近的 CYPOR 结构和生物物理研究表明，两个黄素结构域在催化过程中经历了大的结构域移动。 NOS 亚型在还原酶结构域内含有额外的调节元件，可通过 Ca2+ 依赖性钙调蛋白 (CaM) 结合控制电子转移。最近的 iNOS Ca2+/CaM-FMN 结构的晶体结构（包含与 Ca2+/CaM 复合的 FMN 结构域）提供了 NOS 还原酶和加氧酶结构域之间连接的结构信息，使得模拟全 iNOS 结构成为可能。这篇综述总结了我们对 CYPOR 催化过程中结构域运动动力学的理解以及 NOS 二黄素还原酶结构域在 NOS 同工酶活性调节中的作用的最新进展。
NADPH-cytochrome P450 oxidoreductase (CYPOR) and nitric oxide synthase (NOS), two members of the diflavin oxidoreductase family, are multi-domain enzymes containing distinct FAD and FMN domains connected by a flexible hinge. FAD accepts a hydride ion from NADPH, and reduced FAD donates electrons to FMN, which in turn transfers electrons to the heme center of cytochrome P450 or NOS oxygenase domain. Structural analysis of CYPOR, the prototype of this enzyme family, has revealed the exact nature of the domain arrangement and the role of residues involved in cofactor binding. Recent structural and biophysical studies of CYPOR have shown that the two flavin domains undergo large domain movements during catalysis. NOS isoforms contain additional regulatory elements within the reductase domain that control electron transfer through Ca2+-dependent calmodulin (CaM) binding. The recent crystal structure of an iNOS Ca2+/CaM-FMN construct, containing the FMN domain in complex with Ca2+/CaM, provided structural information on the linkage between the reductase and oxgenase domains of NOS, making it possible to model the holo iNOS structure. This review summarizes recent advances in our understanding of the dynamics of domain movements during CYPOR catalysis and the role of the NOS diflavin reductase domain in the regulation of NOS isozyme activities.
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影响因子：
15
作者：
Chang, Chih-Wei;He, Ting-Fang;Guo, Lijun;Stevens, Jeffrey A.;Li, Tanping;Wang, Lijuan;Zhong, Dongping
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影响因子：
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通讯作者：
Shackleton, CHL
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4.8
作者：
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通讯作者：
Daff, S
影响因子：
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作者：
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通讯作者：
Getzoff, ED