Probing inducible nitric oxide synthase with a pterin-ruthenium(II) sensitizer wire.
Probing inducible nitric oxide synthase with a pterin-ruthenium(II) sensitizer wire.
复制标题
使用蝶呤-钌 (II) 敏化线探测诱导型一氧化氮合酶。
DOI：
10.1002/anie.200703743
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Goodin,DavidB
中科院分区：
文献类型：
--
作者：
Glazer,EdithC;Nguyen,YenHoangLe;Gray,HarryB;Goodin,DavidB
Nitric oxide synthase (NOS) is the primary biological source of the ubiquitous signaling molecule, nitric oxide (• NO). The enzyme utilizes tetrahydrobiopterin (H4B) as an essential cofactor, where it plays a key role in the catalytic conversion of L-arginine to citrulline and• NO. 1 The pterin has been shown to serve both structural and catalytic roles in the enzyme by affecting the monomer to dimer transition, promoting protein stability, and forming a radical cation during catalytic turnover. 2We have previously developed redox-active sensitizer wires to probe the active sites of heme enzymes. 3 In this report, we describe a new class of redox-active wires that target the pterin binding site of NOS. The pterin lies adjacent to the heme, and directly interacts with the catalytic center through hydrogen bonds to the heme propionate group. It is close in space, but physically distinct from the face of the heme containing the arginine binding site, allowing both cofactor and substrate to bind simultanously. 4, 5 Thus, introducing a molecular wire at the pterin site may allow photochemical triggering of enzyme turnover, thereby offering an opportunity to study catalytic intermediates and to shed new light on the cofactor’s role in catalysis. 6 Here we report the design and synthesis of a Ru (II)-pterin wire, and investigate its interaction with the heme domain of murine inducible nitric oxide synthase (iNOSheme).
