title: Invertebrate hemoglobins and nitric oxide: how heme pocket structure controls reactivity.
abstract: Hemoglobins (Hbs), generally defined as 5 or 6 coordinate heme proteins whose primary function is oxygen transport, are now recognized to occur in virtually all phyla of living organisms. Historically, study of their function focused on oxygen as a reversibly bound ligand of the ferrous form of the protein. Other diatomic ligands like carbon monoxide and nitric oxide were considered "non-physiological" but useful probes of structure-function relationships in Hbs. This investigatory landscape changed dramatically in the 1980s when nitric oxide was discovered to activate a heme protein, cyclic guanylate cyclase. Later, its activation was likened to Perutz' description of Hb's allosteric properties being triggered by a ligand-dependent "out-of-plane/into-plane" movement of the heme iron. In 1996, a functional role for nitric oxide in human and mammalian Hbs was demonstrated and since that time, the interest in NO as a physiologically relevant Hb ligand has greatly increased. Concomitantly, non-oxygen binding properties of Hbs have challenged the view that Hbs arose for their oxygen storage and transport properties. In this focused review we discuss some invertebrate Hbs' functionally significant reactions with nitric oxide and how strategic positioning of a few residues in the heme pocket plays an large role in the interplay of diatomic ligands to ferrous and ferric heme iron in these proteins.
authors.affiliation: Stokes Research Institute, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gow
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Payson
authors.forename: Joseph
authors.initials: J
authors.lastname: Bonaventura
mesh_terms: D000495:Allosteric Site; D000818:Animals; D001665:Binding Sites; D005290:Ferric Compounds / Q000737:chemistry / Q000378:metabolism; D005296:Ferrous Compounds / Q000737:chemistry / Q000378:metabolism; D006418:Heme / Q000737:chemistry* / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007448:Invertebrates; D008024:Ligands; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D005290:Ferric Compounds; D005296:Ferrous Compounds; D006454:Hemoglobins; D008024:Ligands; D009569:Nitric Oxide; D006418:Heme; D010100:Oxygen