Structure of nitric oxide synthase oxygenase dimer with pterin and substrate
Structure of nitric oxide synthase oxygenase dimer with pterin and substrate
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DOI：
10.1126/science.279.5359.2121
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发表时间：
1998-03-27
期刊：
影响因子：
56.9
通讯作者：
Tainer, JA
中科院分区：
文献类型：
--
作者：
Crane, BR;Arvai, AS;Tainer, JA
具有活性中心水分子、底物L-精氨酸（L-Arg）或产物类似物硫代瓜氨酸的鼠精氨酸诱导型一氧化氮合酶加氧酶二聚体的晶体结构揭示了二聚化、辅因子四氢生物蝶呤和L-Arg结合如何完成合成基本生物信号和细胞毒素一氧化氮的催化中心。蝶呤结合重折叠中央界面区，招募新的结构元件，创建一个30埃深的活性中心通道，并导致35度螺旋倾斜，暴露血红素边缘和相邻残基色氨酸-366，用于可能的还原酶结构域相互作用和小窝蛋白抑制。血红素丙酸酯与蝶呤和L-Arg的相互作用表明蝶呤对血红素结合氧具有电子影响。L-精氨酸与谷氨酸-371结合，并与血红素堆叠在疏水口袋中，以通过直接质子捐赠来帮助激活血红素结合的氧，从而区分一氧化氮合成的两个化学步骤。
Crystal structures of the murine cytokine-inducible nitric oxide synthase oxygenase dimer with active-center water molecules, the substrate L-arginine (L-Arg), or product analog thiocitrulline reveal how dimerization, cofactor tetrahydrobiopterin, and L-Arg binding complete the catalytic center for synthesis of the essential biological signal and cytotoxin nitric oxide. Pterin binding refolds the central interface region, recruits new structural elements, creates a 30 angstrom deep active-center channel, and causes a 35 degrees helical tilt to expose a heme edge and the adjacent residue tryptophan-366 for likely reductase domain interactions and caveolin inhibition. Heme propionate interactions with pterin and L-Arg suggest that pterin has electronic influences on heme-bound oxygen. L-Arginine binds to glutamic acid-371 and stacks with heme in an otherwise hydrophobic pocket to aid activation of heme-bound oxygen by direct proton donation and thereby differentiate the two chemical steps of nitric oxide synthesis.