The structure of nitric oxide synthase oxygenase domain and inhibitor complexes
The structure of nitric oxide synthase oxygenase domain and inhibitor complexes
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DOI：
10.1126/science.278.5337.425
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发表时间：
1997-10-17
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
一氧化氮合酶加氧酶结构域 (NOSox) 氧化精氨酸以合成细胞信号和防御性细胞毒素一氧化氮 (NO)。细胞因子诱导型 NOSox 的晶体结构测定揭示了一种不寻常的折叠和血红素环境，可稳定催化关键的活性氧中间体。带翼的β片层产生弯曲的α-β域，类似于棒球接球手的手套，血红素紧握在手掌中。暴露的疏水残基的位置和突变分析的结果将二聚体界面置于血红素结合袋附近。并列的疏水性 O-2- 和极性 L-精氨酸结合位点分别由咪唑和氨基胍占据，为设计双功能抑制剂提供了模板，并意味着底物辅助催化。
The nitric oxide synthase oxygenase domain (NOSox) oxidizes arginine to synthesize the cellular signal and defensive cytotoxin nitric oxide (NO). Crystal structures determined for cytokine-inducible NOSox reveal an unusual fold and heme environment for stabilization of activated oxygen intermediates key for catalysis. A winged beta sheet engenders a curved alpha-beta domain resembling a baseball catcher's mitt with heme clasped in the palm. The location of exposed hydrophobic residues and the results of mutational analysis place the dimer interface adjacent to the heme-binding pocket. Juxtaposed hydrophobic O-2- and polar L-arginine-binding sites occupied by imidazole and aminoguanidine, respectively, provide a template for designing dual-function inhibitors and imply substrate-assisted catalysis.