1zor
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Isocitrate dehydrogenase from the hyperthermophile Thermotoga maritima
OverviewOverview
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.
About this StructureAbout this Structure
1ZOR is a Single protein structure of sequence from Thermotoga maritima with as ligand. Active as Isocitrate dehydrogenase (NADP(+)), with EC number 1.1.1.42 Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of a hyperthermostable subfamily II isocitrate dehydrogenase from Thermotoga maritima., Karlstrom M, Steen IH, Madern D, Fedoy AE, Birkeland NK, Ladenstein R, FEBS J. 2006 Jul;273(13):2851-68. Epub 2006 Jun 5. PMID:16759231
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