Activity, Stability and Structural Studies of Lactate Dehydrogenases Adapted to Extreme Thermal Environments

Stepwise Adaptations to Low Temperature as Revealed by Multiple Mutants of Psychrophilic α-Amylase from Antarctic Bacterium

“…The prevailing hypothesis assumes that cold-adapted enzymes have acquired a high catalytic activity at low temperature by improving their conformational flexibility at the expense of stability (7)(8)(9)(10). It has been shown that the crystal structure of psychrophilic enzymes is characterized by the disappearance of various noncovalent stabilizing interactions, resulting in both an improved dynamics of the enzyme conformation and in a weak stability (11)(12)(13)(14)(15)(16)(17). There is indeed a clear decrease in the number and strength of all known weak interactions and structural factors involved in protein stability, from thermophiles, mesophiles to psychrophiles (17)(18)(19).…”

The Core of Allosteric Motion in Thermus caldophilus l-Lactate Dehydrogenase

“…7B), although the crucial thermal stability of BlLDH has not been examined. It was reported that TtLDH (27) and T. maritima LDH (41), another hyperthermostable LDH (49), have increased numbers of intersubunit hydrogen bonds or salt bridges as compared with heatlabile LDHs. Nevertheless, TcLDH has an equivalent number of intersubunit hydrogen bonds (15-16 per monomer) to that of LcLDH (15 per monomer) and an even markedly lower number than that of LpLDH (26 per monomer).…”

“…This L value is markedly greater than the value for LcLDH (3.0 ϫ 10 2 ) (16) and is reduced to 6.8 by the P2 mutation (R173Q/R216L) (25). Recently, the apo and holo structures of Thermus thermophilus LDH (TtLDH), which only has the A154G and H179Y replacements of TcLDH, were determined (27). However, TtLDH exhibits only a 10-fold increased K m value for pyruvate in the absence of FBP at pH 7.0 and 30°C, and the 1-Mut (R218A) and 5-Mut (R79W, R151A, E279A, E313A, and E299A) mutant TtLDHs exhibit ϳ2-and 3.6-fold reduced K m values in the absence of FBP, respectively (28).…”

Functional and adaptive significance of differentially expressed lactate dehydrogenase isoenzymes in tissues of four obligatory air-breathing Channa species

“…Apparently, there are two classes of such variations in distribution of isoenzymes: (1) those where subunit restriction leads to preferential combination or association of LDH subunits (McGovern & Tracy 1981;Fields et al 1989;Coquelle et al 2007); or (2) those that have restricted tissue expressions, such as the expression of LDH-C in the eye of C. gachua (Murphy & Crabtree 1985;Murphy et al 1990). The former class is under the influence of some adaptive strategy based on their metabolic demands, aerobic or anaerobic.…”