Structure and Function of Lactate Dehydrogenase from Hagfish

Yoshikazu Nishiguchi,Nobue Ito,Mitsumasa Okada

doi:10.3390/md8030594

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.

Highlights

The deep sea is characterized by low temperature (1–4 °C), extremely high hydrostatic pressure, lack of sunlight, and relatively low influx of utilizable organic material derived from primary production in surface waters
We investigated the pressure-adaptive mechanism of lactate dehydrogenases (LDHs) from hagfish and considered the relationship between this mechanism and human disease
The B4 isozyme was expressed in the hearts of the two hagfish

Summary

Introduction

The deep sea is characterized by low temperature (1–4 °C), extremely high hydrostatic pressure, lack of sunlight, and relatively low influx of utilizable organic material derived from primary production in surface waters. Among such environmental factors, hydrostatic pressure is thought to have the greatest influence on the vertical distribution of organisms and speciation in the deep seas [1,2,3] and on the formation of protein complexes, e.g., enzyme–substrate or protein–protein interactions [4]. The results of circular dichroism spectroscopic analysis pointed to protein unfolding as the cause of inactivation [9] In those studies, the amino acids responsible for the adaptation were not identified

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Conclusion