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

Abstract

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, which is an important step for NO-dependent signaling. In the five-coordinate nitrosyl complex, NO can reside either on 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, the Shewanella oneidensis H-NOX (So H-NOX)–NO complex was biophysically characterized under limiting and excess NO. The results show that So H-NOX preferably forms a distal NO species under 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 return of the histidine ligand to the heme.