Regulation of nitric oxide signaling by formation of a distal receptor-ligand complex

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.

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / isolation & purification
  • Bacterial Proteins / metabolism*
  • Histidine Kinase / antagonists & inhibitors
  • Histidine Kinase / metabolism
  • Ligands
  • Models, Molecular
  • Nitric Oxide / chemistry
  • Nitric Oxide / metabolism*
  • Shewanella / metabolism*
  • Signal Transduction*


  • Bacterial Proteins
  • Ligands
  • Nitric Oxide
  • Histidine Kinase