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PDBsum entry 1zor
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Oxidoreductase
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PDB id
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1zor
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References listed in PDB file
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Key reference
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Title
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The crystal structure of a hyperthermostable subfamily ii isocitrate dehydrogenase from thermotoga maritima.
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Authors
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M.Karlström,
I.H.Steen,
D.Madern,
A.E.Fedöy,
N.K.Birkeland,
R.Ladenstein.
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Ref.
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Febs J, 2006,
273,
2851-2868.
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PubMed id
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Abstract
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Isocitrate dehydrogenase (IDH) from the hyperthermophile Thermotoga maritima
(TmIDH) catalyses NADP+- and metal-dependent oxidative decarboxylation of
isocitrate to alpha-ketoglutarate. It belongs to the beta-decarboxylating
dehydrogenase family and is the only hyperthermostable IDH identified within
subfamily II. Furthermore, it is the only IDH that has been characterized as
both dimeric and tetrameric in solution. We solved the crystal structure of the
dimeric apo form of TmIDH at 2.2 A. The R-factor of the refined model was 18.5%
(R(free) 22.4%). The conformation of the TmIDH structure was open and showed a
domain rotation of 25-30 degrees compared with closed IDHs. The separate domains
were found to be homologous to those of the mesophilic mammalian IDHs of
subfamily II and were subjected to a comparative analysis in order to find
differences that could explain the large difference in thermostability.
Mutational studies revealed that stabilization of the N- and C-termini via
long-range electrostatic interactions were important for the higher
thermostability of TmIDH. Moreover, the number of intra- and intersubunit ion
pairs was higher and the ionic networks were larger compared with the mesophilic
IDHs. Other factors likely to confer higher stability in TmIDH were a less
hydrophobic and more charged accessible surface, a more hydrophobic subunit
interface, more hydrogen bonds per residue and a few loop deletions. The
residues responsible for the binding of isocitrate and NADP+ were found to be
highly conserved between TmIDH and the mammalian IDHs and it is likely that the
reaction mechanism is the same.
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