title: The structure of Ascaris hemoglobin domain I at 2.2 A resolution: molecular features of oxygen avidity.
abstract: The perienteric hemoglobin of the parasitic nematode Ascaris has an exceptionally high affinity for oxygen. It is an octameric protein containing two similar heme-binding domains per subunit, but recombinant constructs expressing a single, monomeric heme-binding domain (domain 1; D1) retain full oxygen avidity. We have solved the crystal structure of D1 at 2.2 A resolution. Analysis of the structure reveals a characteristic globin fold and illuminates molecular features involved in oxygen avidity of Ascaris perienteric hemoglobin. A strong hydrogen bond between tyrosine at position 10 in the B helix (tyrosine-B10) and the distal oxygen of the ligand, combined with a weak hydrogen bond between glutamine-E7 and the proximal oxygen, grips the ligand in the binding pocket. A third hydrogen bond between these two amino acids appears to stabilize the structure. The B helix of D1 is displaced laterally by 2.5 A when compared with sperm whale myoglobin. This shifts the tyrosine-B10 hydroxyl far enough from liganded oxygen to form a strong hydrogen bond without steric hindrance. Changes in the F helix compared with myoglobin contribute to a tilted heme that may also be important for oxygen affinity.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: A P
authors.initials: AP
authors.lastname: Kloek
authors.forename: D E
authors.initials: DE
authors.lastname: Goldberg
authors.forename: F S
authors.initials: FS
authors.lastname: Mathews
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001200:Ascaris / Q000378:metabolism*; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D006418:Heme / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D006639:Histidine; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009211:Myoglobin / Q000737:chemistry; D010100:Oxygen; D010108:Oxyhemoglobins / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012984:Software; D014907:Whales
chemical_list: D006454:Hemoglobins; D009211:Myoglobin; D010108:Oxyhemoglobins; D011994:Recombinant Proteins; D006418:Heme; D006639:Histidine; D010100:Oxygen