Crystallographic studies on endothelial nitric oxide synthase complexed with nitric oxide and mechanism-based inhibitors.
Crystallographic studies on endothelial nitric oxide synthase complexed with nitric oxide and mechanism-based inhibitors.
复制标题
与一氧化氮复合的内皮一氧化氮合酶和基于机制的抑制剂的晶体学研究。
DOI：
10.1021/bi002658v
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发表时间：
2001
期刊：
影响因子：
2.9
通讯作者：
Poulos,TL
中科院分区：
文献类型：
--
作者：
Li,H;Raman,CS;Martásek,P;Masters,BS;Poulos,TL
内皮型一氧化氮合酶（NOS）血红素结构域与NO络合的晶体结构揭示了NO与底物l-精氨酸末端胍基氮之间密切的氢键相互作用。预计双氧也会以类似的模式结合，这将有助于质子从l- arg提取到双氧，这是O−O键裂解的必要步骤。基于机制的NOS抑制剂N5-（1-亚氨基乙基）-l-鸟氨酸和n -（3-（氨基甲基）苄基）乙酰脒的结构，为这类化合物如何作为自杀底物抑制剂导致血红素氧化提供了线索。
The crystal structure of the endothelial nitric oxide synthase (NOS) heme domain complexed with NO reveals close hydrogen bonding interactions between NO and the terminal guanidino nitrogen of the substrate,l-arginine. Dioxygen is expected to bind in a similar mode which will facilitate proton abstraction froml-Arg to dioxygen, a required step for O−O bond cleavage. Structures of mechanism-based NOS inhibitors,N5-(1-iminoethyl)-l-ornithine andN-(3-(aminomethyl)benzyl)acetamidine, provide clues on how this class of compounds operate as suicide substrate inhibitors leading to heme oxidation.