THE STRUCTURE OF ASCARIS HEMOGLOBIN DOMAIN-I AT 2.2 ANGSTROM RESOLUTION - MOLECULAR-FEATURES OF OXYGEN AVIDITY

The perienteric hemoglobin of the parasitic nematode Ascaris has an ex ceptionally high affinity for oxygen. It is an octameric protein conta ining two similar hemebinding domains per subunit, but recombinant con structs expressing a single, monomeric heme-binding domain (domain 1; D1) retain full oxygen avidity. We have solved the crystal structure o f D1 at 2.2 Angstrom resolution. Analysis of the structure reveals a c haracteristic 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) an d 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 ap pears to stabilize the structure. The B helix of D1 is displaced later ally by 2.5 Angstrom when compared with sperm whale myoglobin. This sh ifts the tyrosine-B10 hydroxyl far enough from liganded oxygen to form a strong hydrogen bond without steric hindrance. Changes in the F hel ix compared with myoglobin contribute to a tilted heme that may also b e important for oxygen affinity.