PDBsum entry 1j1w

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Oxidoreductase PDB id
Protein chains
738 a.a. *
NAP ×4
Waters ×445
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of the monomeric isocitrate dehydrogenase in complex with NADP+
Structure: Isocitrate dehydrogenase. Chain: a, b, c, d. Ec:
Source: Azotobacter vinelandii. Organism_taxid: 354. Strain: iam1078
3.20Å     R-factor:   0.260     R-free:   0.297
Authors: Y.Yasutake,S.Watanabe,M.Yao,Y.Takada,N.Fukunaga,I.Tanaka
Key ref:
Y.Yasutake et al. (2003). Crystal structure of the monomeric isocitrate dehydrogenase in the presence of NADP+: insight into the cofactor recognition, catalysis, and evolution. J Biol Chem, 278, 36897-36904. PubMed id: 12855708 DOI: 10.1074/jbc.M304091200
19-Dec-02     Release date:   23-Sep-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P16100  (IDH_AZOVI) -  Isocitrate dehydrogenase [NADP]
741 a.a.
738 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

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

Citric acid cycle
      Reaction: Isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH
Bound ligand (Het Group name = NAP)
corresponds exactly
= 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!
  Cellular component     cytoplasm   1 term 
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     oxidoreductase activity     4 terms  


DOI no: 10.1074/jbc.M304091200 J Biol Chem 278:36897-36904 (2003)
PubMed id: 12855708  
Crystal structure of the monomeric isocitrate dehydrogenase in the presence of NADP+: insight into the cofactor recognition, catalysis, and evolution.
Y.Yasutake, S.Watanabe, M.Yao, Y.Takada, N.Fukunaga, I.Tanaka.
NADP+-dependent monomeric isocitrate dehydrogenase (IDH) from the nitrogen-fixing bacterium Azotobacter vinelandii (AvIDH) is one of members of the beta-decarboxylating dehydrogenase family and catalyzes the dehydration and decarboxylation of isocitrate to yield 2-oxoglutrate and CO2 in the Krebs cycle. We solved the crystal structure of the AvIDH in complex with cofactor NADP+ (AvIDH-NADP+ complex). The final refined model shows the closed form that has never been detected in any previously solved structures of beta-decarboxylating dehydrogenases. The structure also reveals all of the residues that interact with NADP+. The structure-based sequence alignment reveals that these residues were not conserved in any other dimeric NADP+-dependent IDHs. Therefore the NADP+ specificity of the monomeric and dimeric IDHs was independently acquired through the evolutional process. The AvIDH was known to show an exceptionally high turnover rate. The structure of the AvIDH-NADP+ complex indicates that one loop, which is not present in the Escherichia coli IDHs, reliably stabilizes the conformation of the nicotinamide mononucleotide of the bound NADP+ by forming a few hydrogen bonds, and such interactions are considered to be important for the monomeric enzyme to initiate the hydride transfer reaction immediately. Finally, the structure of the AvIDH is compared with that of other dimeric NADP-IDHs. Several structural features demonstrate that the monomeric IDHs are structurally more related to the eukaryotic dimeric IDHs than to the bacterial dimeric IDHs.
  Selected figure(s)  
Figure 2.
FIG. 2. Structural comparison between the open and closed form of the AvIDH. A, the previous structure of the AvIDH-isocitrate-Mn2+ complex. B, the present structure of the AvIDH-NADP+ complex. The AvIDH-NADP+ complex showed a more closed form than the previous AvIDH-isocitrate-Mn2+ complex by the rigid-body domain movement. Although the crystal of the AvIDH was obtained in a solution containing isocitrate and Ca^2+, the isocitrate and Ca^2+ were not found in the present closed structure. The molecular surfaces were generated using the program GRASP (62).
Figure 4.
FIG. 4. The NADP+ recognition site of the AvIDH and EcIDH. A, the stereoview of the NADP+ recognition site of the AvIDH. The specificity for NADP+ is primarily conferred by the interactions between His589, Arg600, and Arg649 and 2'-phosphomonoester. The residues Asn85, Ser87, and Ser585 also interact with the nicotinamide mononucleotide, and these interactions play a role in stabilizing the conformation of the nicotinamide ring moiety of bound NADP+. B, the stereoview of the NADP+ recognition site of the EcIDH (PDB code 1AI2 [PDB] ). Three residues, Tyr345, Tyr391, and Arg395, which are not conserved in the AvIDH, recognize the 2'-phosphomonoester. The residues structurally corresponding to Asn85 and Ser87 of the AvIDH are not present in the EcIDH. The figures were generated using the program MOLSCRIPT (60) and Raster3D (61).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 36897-36904) copyright 2003.  
  Figures were selected by an automated process.  

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
16416443 F.Imabayashi, S.Aich, L.Prasad, and L.T.Delbaere (2006).
Substrate-free structure of a monomeric NADP isocitrate dehydrogenase: an open conformation phylogenetic relationship of isocitrate dehydrogenase.
  Proteins, 63, 100-112.
PDB code: 2b0t
16489454 K.Gao, Q.Song, and D.Wei (2006).
Coupling of enantioselective biooxidation of DL-1,2-propanediol and bioreduction of pinacolone via regeneration cycle of coenzyme.
  Appl Microbiol Biotechnol, 71, 819-823.  
16795038 N.E.Ward, N.R.Pellis, S.A.Risin, and D.Risin (2006).
Gene expression alterations in activated human T-cells induced by modeled microgravity.
  J Cell Biochem, 99, 1187-1202.  
16284723 A.Rodríguez-Arnedo, M.Camacho, F.Llorca, and M.J.Bonete (2005).
Complete reversal of coenzyme specificity of isocitrate dehydrogenase from Haloferax volcanii.
  Protein J, 24, 259-266.  
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.