Guo Yirui, Suess Daniel L M, Herzik Mark A, Iavarone Anthony T, Britt R David, Marletta Michael A
California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California, USA.
Department of Chemistry, University of California, Davis, Davis, California, USA.
Nat Chem Biol. 2017 Dec;13(12):1216-1221. doi: 10.1038/nchembio.2488. Epub 2017 Oct 2.
The binding of nitric oxide (NO) to the heme cofactor of heme-nitric oxide/oxygen binding (H-NOX) proteins can lead to the dissociation of the heme-ligating histidine residue and yield a five-coordinate nitrosyl complex, an important step for NO-dependent signaling. In the five-coordinate nitrosyl complex, NO can reside on either the distal or proximal side of the heme, which could have a profound influence over the lifetime of the in vivo signal. To investigate this central molecular question, we characterized the Shewanella oneidensis H-NOX (So H-NOX)-NO complex biophysically under limiting and excess NO conditions. The results show that So H-NOX preferably forms a distal NO species with both limiting and excess NO. Therefore, signal strength and complex lifetime in vivo will be dictated by the dissociation rate of NO from the distal complex and the rebinding of the histidine ligand to the heme.
一氧化氮（NO）与血红素 - 一氧化氮/氧气结合（H - NOX）蛋白的血红素辅因子结合，可导致血红素连接组氨酸残基解离，生成五配位亚硝酰配合物，这是NO依赖性信号传导的重要步骤。在五配位亚硝酰配合物中，NO可位于血红素的远端或近端，这可能对体内信号的寿命产生深远影响。为了研究这个核心分子问题，我们在有限和过量NO条件下对希瓦氏菌H - NOX（So H - NOX）-NO配合物进行了生物物理表征。结果表明，So H - NOX在有限和过量NO条件下均优先形成远端NO物种。因此，体内的信号强度和配合物寿命将由NO从远端配合物的解离速率以及组氨酸配体与血红素的重新结合来决定。
