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.