A molecular basis for NO selectivity in soluble guanylate cyclase

Nat Chem Biol. 2005 Jun;1(1):53-9. doi: 10.1038/nchembio704. Epub 2005 May 24.


Soluble guanylate cyclases (sGCs) function as heme sensors that selectively bind nitric oxide (NO), triggering reactions essential to animal physiology. Recent discoveries place sGCs in the H-NOX family (heme nitric oxide/oxygen-binding domain), which includes bacterial proteins from aerobic and anaerobic organisms. Some H-NOX proteins tightly bind oxygen (O2), whereas others show no measurable affinity for O2, providing the basis for selective NO signaling in aerobic cells. Using a series of wild-type and mutant H-NOXs, we established a molecular basis for ligand discrimination. A distal pocket tyrosine is requisite for O2 binding in the H-NOX family. These data suggest that sGC uses a kinetic selection against O2; we propose that the O2 dissociation rate in the absence of this tyrosine is fast and that a stable O2 complex does not form.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Binding, Competitive
  • Biosensing Techniques
  • Guanylate Cyclase
  • Hemeproteins / chemistry*
  • Hemeproteins / metabolism
  • Ligands
  • Molecular Sequence Data
  • Nitric Oxide / chemistry*
  • Oxygen / chemistry*
  • Protein Conformation
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Sequence Alignment
  • Soluble Guanylyl Cyclase
  • Thermoanaerobacterium / chemistry


  • Bacterial Proteins
  • Hemeproteins
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Nitric Oxide
  • Guanylate Cyclase
  • Soluble Guanylyl Cyclase
  • Oxygen