Ligand discrimination in soluble guanylate cyclase and the H-NOX family of heme sensor proteins

Curr Opin Chem Biol. 2005 Oct;9(5):441-6. doi: 10.1016/j.cbpa.2005.08.015.


Soluble guanylate cyclases (s GC s) are eukaryotic heme sensor proteins that selectively bind NO in the presence of a large excess of the similar diatomic gas, O(2); this discrimination is essential for NO signaling. Recent discoveries place sGC in the H-NOX (heme nitric oxide and/or oxygen binding domain) family that includes bacterial proteins. The defining characteristic of this family is that some H-NOX proteins tightly bind O(2) whereas others, such as sGC, show no measurable affinity for O(2). A molecular basis for this ligand selectivity has now been established. A distal pocket tyrosine is requisite for O(2) binding and is used to kinetically distinguish between NO and O(2). In the absence of this tyrosine, the O(2) dissociation rate is so fast that the O(2) complex is never formed, whereas the rate of NO dissociation remains essentially unchanged, thus providing discrimination.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Guanylate Cyclase
  • Hemeproteins / chemistry
  • Hemeproteins / metabolism*
  • Humans
  • Ligands
  • Molecular Sequence Data
  • Oxygen / metabolism
  • Protein Conformation
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Soluble Guanylyl Cyclase
  • Tyrosine / metabolism


  • Hemeproteins
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Tyrosine
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase
  • Oxygen