Ligand specificity of H-NOX domains: from sGC to bacterial NO sensors

J Inorg Biochem. 2005 Apr;99(4):892-902. doi: 10.1016/j.jinorgbio.2004.12.016.


Soluble guanylate cyclase (sGC) is a nitric oxide (NO) sensing hemoprotein that has been found in eukaryotes from Drosophila to humans. Prokaryotic proteins with significant homology to the heme domain of sGC have recently been identified through genomic analysis. This family of heme proteins has been named the H-NOX domain, for Heme-Nitric oxide/OXygen binding domain. The key observation from initial studies in this family is that some members, those proteins from most eukaryotes and facultative aerobic prokaryotes, bind NO in a five-coordinate heme complex, but do not bind oxygen (O(2)), the same ligand binding characteristics as sGC. H-NOX family members from obligate aerobic prokaryotes bind O(2) and NO in six-coordinate complexes, similar to the globins and other O(2)-sensing heme proteins. The molecular factors that contribute to these differences in ligand specificity, within a family of sequence related proteins, are the subject of this review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / metabolism
  • Biosensing Techniques*
  • Drosophila / enzymology
  • Genomics
  • Guanylate Cyclase / chemistry
  • Guanylate Cyclase / genetics
  • Guanylate Cyclase / metabolism*
  • Heme / chemistry*
  • Ligands
  • Molecular Sequence Data
  • Nitric Oxide / chemistry*
  • Oxygen / chemistry
  • Prokaryotic Cells / metabolism
  • Protein Binding
  • Sequence Alignment


  • Bacterial Proteins
  • Ligands
  • Nitric Oxide
  • Heme
  • Guanylate Cyclase
  • Oxygen