title: A molecular basis for NO selectivity in soluble guanylate cyclase.
abstract: 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.
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Boon
authors.forename: Shirley H
authors.initials: SH
authors.lastname: Huang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Marletta
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001667:Binding, Competitive; D015374:Biosensing Techniques; D006162:Guanylate Cyclase; D006420:Hemeproteins / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D011487:Protein Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D000071756:Soluble Guanylyl Cyclase; D046950:Thermoanaerobacterium / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D006420:Hemeproteins; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D010100:Oxygen