Structure-function relationships in unusual nonvertebrate globins.
Based on the literature and our own results, this review summarizes the most recent state of nonvertebrate myoglobin (Mb) and hemoglobin (Hb) research, not as a general survey of the subject but as a case study. For this purpose, we have selected here four typical globins to discuss their unique structures and properties in detail. These include Aplysia myoglobin, which served as a prototype for the unusual globins lacking the distal histidine residue; midge larval hemoglobin showing a high degree of polymorphism; Tetrahymena hemoglobin evolved with a truncated structure; and yeast flavohemoglobin carrying an enigmatic two-domain structure. These proteins are not grouped by any common features other than the fact they have globin domains and heme groups. As a matter of course, various biochemical functions other than the conventional oxygen transport or storage have been proposed so far to these primitive or ancient hemoglobins or myoglobins, but the precise in vivo activity is still unclear. In this review, special emphasis is placed on the stability properties of the heme-bound O2. Whatever the possible roles of nonvertebrate myoglobins and hemoglobins may be (or might have been), the binding of molecular oxygen to iron(II) must be the primary event to manifest their physiological functions in vivo. However, the reversible and stable binding of O2 to iron(II) is not a simple process, since the oxygenated form of Mb or Hb is oxidized easily to its ferric met-form with the generation of superoxide anion. The metmyoglobin or methemoglobin thus produced cannot bind molecular oxygen and is therefore physiologically inactive. In this respect, protozoan ciliate myoglobin and yeast flavohemoglobin are of particular interest in their very unique structures. Indeed, both proteins have been found to have completely different strategies for overcoming many difficulties in the reversible and stable binding of molecular oxygen, as opposed to the irreversible oxidation of heme iron(II). Such comparative studies of the stability of MbO2 or HbO2 are of primary importance, not only for a full understanding of the globin evolution, but also for planning new molecular designs for synthetic oxygen carriers that may be able to function in aqueous solution and at physiological temperature.
Shikama
Keiji
K
Biological Institute, Graduate School of Life Sciences, Tohoku University, Sendai, Japan. shikama@mail.tains.tohoku.ac.jp
Matsuoka
Ariki
A
D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000737:chemistry* / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000378:metabolism; D005914:Globins / Q000737:chemistry* / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry / Q000235:genetics; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D019476:Insect Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009211:Myoglobin / Q000737:chemistry; D010802:Phylogeny; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D005656:Fungal Proteins; D006454:Hemoglobins; D019476:Insect Proteins; D009211:Myoglobin; D015800:Protozoan Proteins; D006639:Histidine; D005914:Globins