Characterization of nitrosoalkane binding and activation of soluble guanylate cyclase.

Journal Article

Soluble guanylate cyclase (sGC) is the primary receptor for the signaling agent nitric oxide (NO). Electronic absorption and resonance Raman spectroscopy were used to show that nitrosoalkanes bind to the heme of sGC to form six-coordinate, low-spin complexes. In the sGC-nitrosopentane complex, a band assigned to an Fe-N stretching vibration is observed at 543 cm(-)(1) which is similar to values reported for other six-coordinate NO-bound hemoproteins. Nitrosoalkanes activate sGC 2-6-fold and synergize with YC-1, a synthetic benzylindazole derivative, to activate the enzyme 11-47-fold. In addition, the observed off-rates of nitrosoalkanes from sGC were found to be dependent on the alkyl chain length. A linear correlation was found between the observed off-rates and the alkyl chain length which suggests that the sGC heme has a large hydrophobic distal ligand-binding pocket. Together, these data show that nitrosoalkanes are a novel class of heme-based sGC activators and suggest that heme ligation is a general requirement for YC-1 synergism.

Full Text

Duke Authors

Cited Authors

  • Derbyshire, ER; Tran, R; Mathies, RA; Marletta, MA

Published Date

  • December 13, 2005

Published In

Volume / Issue

  • 44 / 49

Start / End Page

  • 16257 - 16265

PubMed ID

  • 16331986

International Standard Serial Number (ISSN)

  • 0006-2960

Digital Object Identifier (DOI)

  • 10.1021/bi0515671

Language

  • eng

Conference Location

  • United States