title: Structure and function of lactate dehydrogenase from hagfish.
abstract: The lactate dehydrogenases (LDHs) in hagfish have been estimated to be the prototype of those in higher vertebrates. The effects of high hydrostatic pressure from 0.1 to 100 MPa on LDH activities from three hagfishes were examined. The LDH activities of Eptatretus burgeri, living at 45-60 m, were completely lost at 5 MPa. In contrast, LDH-A and -B in Eptatretus okinoseanus maintained 70% of their activities even at 100 MPa. These results show that the deeper the habitat, the higher the tolerance to pressure. To elucidate the molecular mechanisms for adaptation to high pressure, we compared the amino acid sequences and three-dimensional structures of LDHs in these hagfish. There were differences in six amino acids (6, 10, 20, 156, 269, and 341). These amino acidresidues are likely to contribute to the stability of the E. okinoseanus LDH under high-pressure conditions. The amino acids responsible for the pressure tolerance of hagfish are the same in both human and hagfish LDHs, and one substitution that occurred as an adaptation during evolution is coincident with that observed in a human disease. Mutation of these amino acids can cause anomalies that may be implicated in the development of human diseases.
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, Japan. guchi@phar.toho-u.ac.jp
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nishiguchi
authors.forename: Nobue
authors.initials: N
authors.lastname: Ito
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Okada
mesh_terms: D000222:Adaptation, Physiological; D000595:Amino Acid Sequence; D000818:Animals; D004795:Enzyme Stability; D006196:Hagfishes / Q000145:classification / Q000502:physiology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D010802:Phylogeny; D011312:Pressure; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013696:Temperature
chemical_list: D007770:L-Lactate Dehydrogenase
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