Department of Chemistry, University of California, Berkeley, CA 94720-3220, USA.
Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19753-60. doi: 10.1073/pnas.0911645106. Epub 2009 Nov 16.
Heme nitric oxide/oxygen (H-NOX) proteins are found in eukaryotes where they are typically part of a larger protein such as soluble guanylate cyclase and in prokaryotes where they are often found in operons with a histidine kinase, suggesting that H-NOX proteins serve as sensors for NO and O(2) in signaling pathways. The Fe(II)-NO complex of the H-NOX protein from Shewanella oneidensis inhibits the autophosphorylation of the operon-associated histidine kinase, whereas the ligand-free H-NOX has no effect on the kinase. NMR spectroscopy was used to determine the structures of the Fe(II)-CO complex of the S. oneidensis H-NOX and the Fe(II)-CO complex of the H103G H-NOX mutant as a mimic of the ligand-free and kinase-inhibitory Fe(II)-NO H-NOX, respectively. The results provide a molecular glimpse into the ligand-induced conformational changes that may underlie kinase inhibition and the subsequent control of downstream signaling.
血红素一氧化氮/氧（H-NOX）蛋白存在于真核生物中，通常是可溶性鸟苷酸环化酶等较大蛋白质的一部分，在原核生物中，它们通常存在于与组氨酸激酶相关的操纵子中，这表明 H-NOX 蛋白作为信号通路中 NO 和 O(2)的传感器。希瓦氏菌属 H-NOX 蛋白的 Fe(II)-NO 复合物抑制操纵子相关组氨酸激酶的自动磷酸化，而无配体的 H-NOX 对激酶没有影响。NMR 光谱用于确定希瓦氏菌属 H-NOX 的 Fe(II)-CO 复合物和 H103G H-NOX 突变体的 Fe(II)-CO 复合物的结构，分别作为无配体和激酶抑制性 Fe(II)-NO H-NOX 的模拟物。结果提供了对配体诱导的构象变化的分子洞察，这些变化可能是激酶抑制和随后对下游信号的控制的基础。
