PDBsum entry 1ika

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Oxidoreductase(NAD(a)-choh(d)) PDB id
Protein chain
414 a.a. *
* Residue conservation analysis
PDB id:
Name: Oxidoreductase(NAD(a)-choh(d))
Title: Structure of isocitrate dehydrogenase with alpha-ketoglutara angstroms resolution: conformational changes induced by decarboxylation of isocitrate
Structure: Isocitrate dehydrogenase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Dimer (from PQS)
2.70Å     R-factor:   0.185    
Authors: B.L.Stoddard,D.E.Koshland Junior
Key ref:
B.L.Stoddard and D.E.Koshland (1993). Structure of isocitrate dehydrogenase with alpha-ketoglutarate at 2.7-A resolution: conformational changes induced by decarboxylation of isocitrate. Biochemistry, 32, 9317-9322. PubMed id: 8369301 DOI: 10.1021/bi00087a009
15-Jun-93     Release date:   31-Jul-94    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08200  (IDH_ECOLI) -  Isocitrate dehydrogenase [NADP]
416 a.a.
414 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(+)
Bound ligand (Het Group name = AKG)
corresponds exactly
+ 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/bi00087a009 Biochemistry 32:9317-9322 (1993)
PubMed id: 8369301  
Structure of isocitrate dehydrogenase with alpha-ketoglutarate at 2.7-A resolution: conformational changes induced by decarboxylation of isocitrate.
B.L.Stoddard, D.E.Koshland.
The structure of the isocitrate dehydrogenase (IDH) complex with bound alpha-ketoglutarate, Ca2+, and NADPH was solved at 2.7-A resolution. The alpha-ketoglutarate binds in the active site at the same position and orientation as isocitrate, with a difference between the two bound molecules of about 0.8 A. The Ca2+ metal is coordinated by alpha-ketoglutarate, three conserved aspartate residues, and a pair of water molecules. The largest motion in the active site relative to the isocitrate enzyme complex is observed for tyrosine 160, which originally forms a hydrogen bond to the labile carboxyl group of isocitrate and moves to form a new hydrogen bond to Asp 307 in the complex with alpha-ketoglutarate. This triggers a number of significant movements among several short loops and adjoining secondary structural elements in the enzyme, most of which participate in dimer stabilization and formation of the active-site cleft. These rearrangements are similar to the ligand-binding-induced movements observed in globins and insulin and serve as a model for an enzymatic mechanism which involves local shifts of secondary structural elements during turnover, rather than large-scale domain closures or loop transitions induced by substrate binding such as those observed in hexokinase or triosephosphate isomerase.

Literature references that cite this PDB file's key reference

  PubMed id Reference
18433062 C.J.Liao, K.H.Chin, C.H.Lin, P.S.Tsai, P.C.Lyu, C.C.Young, A.H.Wang, and S.H.Chou (2008).
Crystal structure of DFA0005 complexed with alpha-ketoglutarate: a novel member of the ICL/PEPM superfamily from alkali-tolerant Deinococcus ficus.
  Proteins, 73, 362-371.
PDB code: 2ze3
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
16407311 A.Hoffmann, F.Merz, A.Rutkowska, B.Zachmann-Brand, E.Deuerling, and B.Bukau (2006).
Trigger factor forms a protective shield for nascent polypeptides at the ribosome.
  J Biol Chem, 281, 6539-6545.  
14563877 C.Merlin, M.Masters, S.McAteer, and A.Coulson (2003).
Why is carbonic anhydrase essential to Escherichia coli?
  J Bacteriol, 185, 6415-6424.  
14512428 T.K.Kim, P.Lee, and R.F.Colman (2003).
Critical role of Lys212 and Tyr140 in porcine NADP-dependent isocitrate dehydrogenase.
  J Biol Chem, 278, 49323-49331.  
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
11953438 A.P.Lin, and L.McAlister-Henn (2002).
Isocitrate binding at two functionally distinct sites in yeast NAD+-specific isocitrate dehydrogenase.
  J Biol Chem, 277, 22475-22483.  
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
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
10677231 C.Weiss, Y.Zeng, J.Huang, M.B.Sobocka, and J.I.Rushbrook (2000).
Bovine NAD+-dependent isocitrate dehydrogenase: alternative splicing and tissue-dependent expression of subunit 1.
  Biochemistry, 39, 1807-1816.  
10739911 K.Thomazeau, R.Dumas, F.Halgand, E.Forest, R.Douce, and V.Biou (2000).
Structure of spinach acetohydroxyacid isomeroreductase complexed with its reaction product dihydroxymethylvalerate, manganese and (phospho)-ADP-ribose.
  Acta Crystallogr D Biol Crystallogr, 56, 389-397.
PDB code: 1qmg
9783749 B.L.Stoddard, B.E.Cohen, M.Brubaker, A.D.Mesecar, and D.E.Koshland (1998).
Millisecond Laue structures of an enzyme-product complex using photocaged substrate analogs.
  Nat Struct Biol, 5, 891-897.
PDB code: 1bl5
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
9211842 A.D.Mesecar, B.L.Stoddard, and D.E.Koshland (1997).
Orbital steering in the catalytic power of enzymes: small structural changes with large catalytic consequences.
  Science, 277, 202-206.
PDB codes: 1ai2 1ai3
9220992 B.E.Cohen, B.L.Stoddard, and D.E.Koshland (1997).
Caged NADP and NAD. Synthesis and characterization of functionally distinct caged compounds.
  Biochemistry, 36, 9035-9044.  
9354646 G.T.Jennings, K.I.Minard, and L.McAlister-Henn (1997).
Expression and mutagenesis of mammalian cytosolic NADP+-specific isocitrate dehydrogenase.
  Biochemistry, 36, 13743-13747.  
9345628 K.Moffat, and Z.Ren (1997).
Synchrotron radiation applications to macromolecular crystallography.
  Curr Opin Struct Biol, 7, 689-696.  
8673602 B.L.Stoddard, A.Dean, and P.A.Bash (1996).
Combining Laue diffraction and molecular dynamics to study enzyme intermediates.
  Nat Struct Biol, 3, 590-595.  
8885829 B.Sankaran, A.J.Chavan, and B.E.Haley (1996).
Identification of adenine binding domain peptides of the NADP+ active site within porcine heart NADP(+)-dependent isocitrate dehydrogenase.
  Biochemistry, 35, 13501-13510.  
8608121 M.J.Brubaker, D.H.Dyer, B.Stoddard, and D.E.Koshland (1996).
Synthesis, kinetics, and structural studies of a photolabile caged isocitrate: a catalytic trigger for isocitrate dehydrogenase.
  Biochemistry, 35, 2854-2864.  
  7836312 B.J.Eikmanns, D.Rittmann, and H.Sahm (1995).
Cloning, sequence analysis, expression, and inactivation of the Corynebacterium glutamicum icd gene encoding isocitrate dehydrogenase and biochemical characterization of the enzyme.
  J Bacteriol, 177, 774-782.  
8548273 G.K.Farber (1995).
Laue crystallography. It's show time.
  Curr Biol, 5, 1088-1090.  
7881901 J.H.Hurley, and A.M.Dean (1994).
Structure of 3-isopropylmalate dehydrogenase in complex with NAD+: ligand-induced loop closing and mechanism for cofactor specificity.
  Structure, 2, 1007-1016.
PDB code: 1hex
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 code is shown on the right.