PDBsum entry 1zor

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protein metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
399 a.a. *
_NA ×2
Waters ×428
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Isocitrate dehydrogenase from the hyperthermophile thermotog
Structure: Isocitrate dehydrogenase. Chain: a, b. Engineered: yes
Source: Thermotoga maritima. Organism_taxid: 243274. Strain: msb8. Gene: tm1148. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.24Å     R-factor:   0.186     R-free:   0.223
Authors: M.Karlstrom,I.H.Steen,N.-K.Birkeland,R.Ladenstein
Key ref: M.Karlström et al. (2006). The crystal structure of a hyperthermostable subfamily II isocitrate dehydrogenase from Thermotoga maritima. FEBS J, 273, 2851-2868. PubMed id: 16759231
13-May-05     Release date:   16-May-06    
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Protein chains
Pfam   ArchSchema ?
Q9X0N2  (Q9X0N2_THEMA) -  Isocitrate dehydrogenase [NADP]
399 a.a.
399 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Isocitrate dehydrogenase (NADP(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Citric acid cycle
      Reaction: Isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH
+ NADP(+)
= 2-oxoglutarate
+ CO(2)
      Cofactor: Mn(2+) or Mg(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     oxidoreductase activity     4 terms  


FEBS J 273:2851-2868 (2006)
PubMed id: 16759231  
The crystal structure of a hyperthermostable subfamily II isocitrate dehydrogenase from Thermotoga maritima.
M.Karlström, I.H.Steen, D.Madern, A.E.Fedöy, N.K.Birkeland, R.Ladenstein.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
18552125 Y.Peng, C.Zhong, W.Huang, and J.Ding (2008).
Structural studies of Saccharomyces cerevesiae mitochondrial NADP-dependent isocitrate dehydrogenase in different enzymatic states reveal substantial conformational changes during the catalytic reaction.
  Protein Sci, 17, 1542-1554.
PDB codes: 2qfv 2qfw 2qfx 2qfy
17692336 A.T.Clark, K.Smith, R.Muhandiram, S.P.Edmondson, and J.W.Shriver (2007).
Carboxyl pK(a) values, ion pairs, hydrogen bonding, and the pH-dependence of folding the hyperthermophile proteins Sac7d and Sso7d.
  J Mol Biol, 372, 992.  
17372193 D.C.Hyatt, B.Youn, Y.Zhao, B.Santhamma, R.M.Coates, R.B.Croteau, and C.Kang (2007).
Structure of limonene synthase, a simple model for terpenoid cyclase catalysis.
  Proc Natl Acad Sci U S A, 104, 5360-5365.
PDB codes: 2ong 2onh
17160675 R.Stokke, D.Madern, A.E.Fedøy, S.Karlsen, N.K.Birkeland, and I.H.Steen (2007).
Biochemical characterization of isocitrate dehydrogenase from Methylococcus capsulatus reveals a unique NAD+-dependent homotetrameric enzyme.
  Arch Microbiol, 187, 361-370.  
17401542 R.Stokke, M.Karlström, N.Yang, I.Leiros, R.Ladenstein, N.K.Birkeland, and I.H.Steen (2007).
Thermal stability of isocitrate dehydrogenase from Archaeoglobus fulgidus studied by crystal structure analysis and engineering of chimers.
  Extremophiles, 11, 481-493.
PDB code: 2iv0
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.