Residues stabilizing the heme moiety of the nitric oxide sensor soluble guanylate cyclase

Soluble guanylate cyclase, a heterodimer consisting of an α- and a heme-containing β-subunit, is the major receptor for the biological messenger nitric oxide (NO) and is involved in various signal transduction pathways. The heme moiety of the enzyme is bound between the axial heme ligand histidine105 and the recently identified counterparts of the heme propionic acids, tyrosine135 and arginine139. The latter residues together with an invariant serine137 form the unique heme binding motif Y-x-S-x-R. In this work, we show that replacement of the serine137 with alanine destabilizes the binding of the heme moiety and impairs NO-mediated soluble guanylate cyclase activation.