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PDBsum entry 2v6b
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Oxidoreductase
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PDB id
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2v6b
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References listed in PDB file
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Key reference
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Title
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Activity, Stability and structural studies of lactate dehydrogenases adapted to extreme thermal environments.
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Authors
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N.Coquelle,
E.Fioravanti,
M.Weik,
F.Vellieux,
D.Madern.
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Ref.
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J Mol Biol, 2007,
374,
547-562.
[DOI no: ]
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PubMed id
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Abstract
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Lactate dehydrogenase (LDH) catalyzes the conversion of pyruvate to lactate with
concomitant oxidation of NADH during the last step in anaerobic glycolysis. In
the present study, we present a comparative biochemical and structural analysis
of various LDHs adapted to function over a large temperature range. The enzymes
were from Champsocephalus gunnari (an Antarctic fish), Deinococcus radiodurans
(a mesophilic bacterium) and Thermus thermophilus (a hyperthermophilic
bacterium). The thermodynamic activation parameters of these LDHs indicated that
temperature adaptation from hot to cold conditions was due to a decrease in the
activation enthalpy and an increase in activation entropy. The crystal
structures of these LDHs have been solved. Pairwise comparisons at the
structural level, between hyperthermophilic versus mesophilic LDHs and
mesophilic versus psychrophilic LDHs, have revealed that temperature adaptation
is due to a few amino acid substitutions that are localized in critical regions
of the enzyme. These substitutions, each having accumulating effects, play a
role in either the conformational stability or the local flexibility or in both.
Going from hot- to cold-adapted LDHs, the various substitutions have decreased
the number of ion pairs, reduced the size of ionic networks, created unfavorable
interactions involving charged residues and induced strong local disorder. The
analysis of the LDHs adapted to extreme temperatures shed light on how
evolutionary processes shift the subtle balance between overall stability and
flexibility of an enzyme.
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Figure 2.
Fig. 2. Ribbon diagram of the apo form of tetrameric TtLDH.
The four monomers are labeled A–D.
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Figure 3.
Fig. 3. A 30 Å slice through a ribbon diagram of a
monomer of TtLDH complexed with oxamate and NADH. The color
scheme used is related to C^α deviation between the apo and
ternary complex. The rainbow scale bar illustrates values of
deviation in angstroms. Inset: RMSD between C^α atoms in the
superimposed subunits of TtLDH (apo versus ternary complex). The
mobile regions (MR) that display the largest deviations are
indicated.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
374,
547-562)
copyright 2007.
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