PDBsum entry 1sjs

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protein links
Oxidoreductase PDB id
Protein chain
415 a.a. *
Waters ×90
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Access to phosphorylation in isocitrate dehydrogenase may oc domain shifting
Structure: Isocitrate dehydrogenase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Homo-Dimer (from PDB file)
2.42Å     R-factor:   0.181     R-free:   0.230
Authors: J.Finer-Moore,R.M.Stroud
Key ref:
J.Finer-Moore et al. (1997). Access to phosphorylation in isocitrate dehydrogenase may occur by domain shifting. Biochemistry, 36, 13890-13896. PubMed id: 9374867 DOI: 10.1021/bi9711691
08-Jul-97     Release date:   03-Dec-97    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08200  (IDH_ECOLI) -  Isocitrate dehydrogenase [NADP]
416 a.a.
415 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!
  Cellular component     cytoplasm   1 term 
  Biological process     oxidation-reduction process   5 terms 
  Biochemical function     oxidoreductase activity     6 terms  


DOI no: 10.1021/bi9711691 Biochemistry 36:13890-13896 (1997)
PubMed id: 9374867  
Access to phosphorylation in isocitrate dehydrogenase may occur by domain shifting.
J.Finer-Moore, S.E.Tsutakawa, D.R.Cherbavaz, D.C.LaPorte, D.E.Koshland, R.M.Stroud.
To clarify further the mechanism of regulation by phosphorylation of isocitrate dehydrogenase, cocrystallization of isocitrate dehydrogenase and isocitrate dehydrogenase kinase/phosphatase in the presence of an ATP analog was attempted. Although cocrystallization was unsuccessful, a new crystal form of isocitrate dehydrogenase was obtained which provides insight into the phosphorylation mechanism. The new, orthorhombic crystal form of isocitrate dehydrogenase is related to the previously reported tetragonal form largely by an approximately 16 degrees shift of a large domain relative to the small domain and clasp region within each subunit of the dimeric enzyme. The NADP+ cofactor binding surface is significantly disrupted by the shift to the open conformation. The solvent-accessible surface area and surface-enclosed volume increase by 2% relative to the dimeric tetragonal form. Most of the increase results from expansion of the active site cleft such that the distance across its opening increases from approximately 5 to 13 A, significantly increasing accessibility to Ser-113. The conformation of isocitrate dehydrogenase in the orthorhombic crystal form more closely resembles that of the crystal structure of the homologous enzyme 3-isopropylmalate dehydrogenase than does the tetragonal isocitrate dehydrogenase conformation. Since the crystal lattice forces are fairly weak, it appears that isocitrate dehydrogenase is a flexible molecule that can easily undergo domain shifts and possibly other induced fit conformational changes, to accommodate binding to isocitrate dehydrogenase kinase/phosphatase.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20505668 J.Zheng, and Z.Jia (2010).
Structure of the bifunctional isocitrate dehydrogenase kinase/phosphatase.
  Nature, 465, 961-965.
PDB codes: 3eps 3lc6 3lcb
17634983 K.Imada, T.Tamura, R.Takenaka, I.Kobayashi, K.Namba, and K.Inagaki (2008).
Structure and quantum chemical analysis of NAD+-dependent isocitrate dehydrogenase: hydride transfer and co-factor specificity.
  Proteins, 70, 63-71.
PDB code: 2d4v
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
17444518 R.Sathyapriya, and S.Vishveshwara (2007).
Structure networks of E. coli glutaminyl-tRNA synthetase: effects of ligand binding.
  Proteins, 68, 541-550.  
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
15146507 J.J.Jeong, T.Sonoda, S.Fushinobu, H.Shoun, and T.Wakagi (2004).
Crystal structure of isocitrate dehydrogenase from Aeropyrum pernix.
  Proteins, 55, 1087-1089.
PDB code: 1v94
15062079 P.P.Iyer, S.H.Lawrence, K.B.Luther, K.R.Rajashankar, H.P.Yennawar, J.G.Ferry, and H.Schindelin (2004).
Crystal structure of phosphotransacetylase from the methanogenic archaeon Methanosarcina thermophila.
  Structure, 12, 559-567.
PDB code: 1qzt
15173171 X.Xu, J.Zhao, Z.Xu, B.Peng, Q.Huang, E.Arnold, and J.Ding (2004).
Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity.
  J Biol Chem, 279, 33946-33957.
PDB codes: 1t09 1t0l
12855708 Y.Yasutake, S.Watanabe, M.Yao, Y.Takada, N.Fukunaga, and I.Tanaka (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.
PDB code: 1j1w
12207025 C.Ceccarelli, N.B.Grodsky, N.Ariyaratne, R.F.Colman, and B.J.Bahnson (2002).
Crystal structure of porcine mitochondrial NADP+-dependent isocitrate dehydrogenase complexed with Mn2+ and isocitrate. Insights into the enzyme mechanism.
  J Biol Chem, 277, 43454-43462.
PDB code: 1lwd
11751849 S.K.Singh, S.P.Miller, A.Dean, L.J.Banaszak, and D.C.LaPorte (2002).
Bacillus subtilis isocitrate dehydrogenase. A substrate analogue for Escherichia coli isocitrate dehydrogenase kinase/phosphatase.
  J Biol Chem, 277, 7567-7573.  
11533060 I.H.Steen, D.Madern, M.Karlström, T.Lien, R.Ladenstein, and N.K.Birkeland (2001).
Comparison of isocitrate dehydrogenase from three hyperthermophiles reveals differences in thermostability, cofactor specificity, oligomeric state, and phylogenetic affiliation.
  J Biol Chem, 276, 43924-43931.  
11284679 S.A.Doyle, P.T.Beernink, and D.E.Koshland (2001).
Structural basis for a change in substrate specificity: crystal structure of S113E isocitrate dehydrogenase in a complex with isopropylmalate, Mg2+, and NADP.
  Biochemistry, 40, 4234-4241.
PDB code: 1hj6
11288177 S.Zhao, D.S.Goodsell, and A.J.Olson (2001).
Analysis of a data set of paired uncomplexed protein structures: new metrics for side-chain flexibility and model evaluation.
  Proteins, 43, 271-279.  
10625615 S.P.Miller, R.Chen, E.J.Karschnia, C.Romfo, A.Dean, and D.C.LaPorte (2000).
Locations of the regulatory sites for isocitrate dehydrogenase kinase/phosphatase.
  J Biol Chem, 275, 833-839.  
9739088 K.Imada, K.Inagaki, H.Matsunami, H.Kawaguchi, H.Tanaka, N.Tanaka, and K.Namba (1998).
Structure of 3-isopropylmalate dehydrogenase in complex with 3-isopropylmalate at 2.0 A resolution: the role of Glu88 in the unique substrate-recognition mechanism.
  Structure, 6, 971-982.
PDB code: 1a05
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.