PDBsum entry 1idc

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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: Isocitrate dehydrogenase from e.Coli (mutant k230m), steady- intermediate complex determined by laue crystallography
Structure: Isocitrate dehydrogenase. Chain: a. Synonym: idh. Engineered: yes. Mutation: yes. Other_details: rate-limited enolate intermediate
Source: Escherichia coli. Organism_taxid: 562. Strain: jlk1. Variant: icd(-) (deficient in wt idh gene). Gene: icd. Expressed in: pembl (dente et al 1983 nuc acids res 11
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.169    
Authors: J.M.Bolduc,D.H.Dyer,W.G.Scott,P.Singer,R.M.Sweet,D.E.Koshlan B.L.Stoddard
Key ref: J.M.Bolduc et al. (1995). Mutagenesis and Laue structures of enzyme intermediates: isocitrate dehydrogenase. Science, 268, 1312-1318. PubMed id: 7761851 DOI: 10.1126/science.7761851
18-Jan-95     Release date:   08-Mar-96    
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
* 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 = OXS)
corresponds exactly
+ 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: 10.1126/science.7761851 Science 268:1312-1318 (1995)
PubMed id: 7761851  
Mutagenesis and Laue structures of enzyme intermediates: isocitrate dehydrogenase.
J.M.Bolduc, D.H.Dyer, W.G.Scott, P.Singer, R.M.Sweet, D.E.Koshland, B.L.Stoddard.
Site-directed mutagenesis and Laue diffraction data to 2.5 A resolution were used to solve the structures of two sequential intermediates formed during the catalytic actions of isocitrate dehydrogenase. Both intermediates are distinct from the enzyme-substrate and enzyme-product complexes. Mutation of key catalytic residues changed the rate determining steps so that protein and substrate intermediates within the overall reaction pathway could be visualized.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21446021 L.B.Bralten, N.K.Kloosterhof, R.Balvers, A.Sacchetti, L.Lapre, M.Lamfers, S.Leenstra, Jonge, J.M.Kros, E.E.Jansen, E.A.Struys, C.Jakobs, G.S.Salomons, S.H.Diks, M.Peppelenbosch, A.Kremer, C.C.Hoogenraad, P.A.Smitt, and P.J.French (2011).
IDH1 R132H decreases proliferation of glioma cell lines in vitro and in vivo.
  Ann Neurol, 69, 455-463.  
20615753 N.K.Kloosterhof, L.B.Bralten, H.J.Dubbink, P.J.French, and M.J.van den Bent (2011).
Isocitrate dehydrogenase-1 mutations: a fundamentally new understanding of diffuse glioma?
  Lancet Oncol, 12, 83-91.  
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
15546978 B.J.Bahnson (2004).
An atomic-resolution mechanism of 3-hydroxy-3-methylglutaryl-CoA synthase.
  Proc Natl Acad Sci U S A, 101, 16399-16400.  
15041745 M.Schmidt, R.Pahl, V.Srajer, S.Anderson, Z.Ren, H.Ihee, S.Rajagopal, and K.Moffat (2004).
Protein kinetics: structures of intermediates and reaction mechanism from time-resolved x-ray data.
  Proc Natl Acad Sci U S A, 101, 4799-4804.
PDB codes: 1s4r 1s4s
12454487 M.Karlström, I.H.Steen, G.Tibbelin, T.Lien, N.K.Birkeland, and R.Ladenstein (2002).
Crystallization and preliminary X-ray structure analysis of isocitrate dehydrogenase from two hyperthermophiles, Aeropyrum pernix and Thermotoga maritima.
  Acta Crystallogr D Biol Crystallogr, 58, 2162-2164.  
12218169 M.L.Baker, I.I.Serysheva, S.Sencer, Y.Wu, S.J.Ludtke, W.Jiang, S.L.Hamilton, and W.Chiu (2002).
The skeletal muscle Ca2+ release channel has an oxidoreductase-like domain.
  Proc Natl Acad Sci U S A, 99, 12155-12160.  
  11206056 R.Chen, and S.S.Jeong (2000).
Functional prediction: identification of protein orthologs and paralogs.
  Protein Sci, 9, 2344-2353.  
11087384 S.A.Doyle, S.Y.Fung, and D.E.Koshland (2000).
Redesigning the substrate specificity of an enzyme: isocitrate dehydrogenase.
  Biochemistry, 39, 14348-14355.  
10489453 G.F.Audette, J.W.Quail, K.Hayakawa, C.Bai, R.Chen, and L.T.Delbaere (1999).
Crystallization and preliminary X-ray diffraction studies of monomeric isocitrate dehydrogenase from Corynebacterium glutamicum.
  Acta Crystallogr D Biol Crystallogr, 55, 1584-1585.  
10572011 S.Wang, K.Karbstein, A.Peracchi, L.Beigelman, and D.Herschlag (1999).
Identification of the hammerhead ribozyme metal ion binding site responsible for rescue of the deleterious effect of a cleavage site phosphorothioate.
  Biochemistry, 38, 14363-14378.  
9891796 A.J.Cozzone (1998).
Regulation of acetate metabolism by protein phosphorylation in enteric bacteria.
  Annu Rev Microbiol, 52, 127-164.  
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
9818266 B.L.Stoddard (1998).
New results using Laue diffraction and time-resolved crystallography.
  Curr Opin Struct Biol, 8, 612-618.  
9671698 G.Zhou, T.Somasundaram, E.Blanc, G.Parthasarathy, W.R.Ellington, and M.S.Chapman (1998).
Transition state structure of arginine kinase: implications for catalysis of bimolecular reactions.
  Proc Natl Acad Sci U S A, 95, 8449-8454.
PDB code: 1bg0
9506521 J.B.Murray, D.P.Terwey, L.Maloney, A.Karpeisky, N.Usman, L.Beigelman, and W.G.Scott (1998).
The structural basis of hammerhead ribozyme self-cleavage.
  Cell, 92, 665-673.
PDB code: 379d
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
10089512 R.B.Ravelli, M.L.Raves, Z.Ren, D.Bourgeois, M.Roth, J.Kroon, I.Silman, and J.L.Sussman (1998).
Static Laue diffraction studies on acetylcholinesterase.
  Acta Crystallogr D Biol Crystallogr, 54, 1359-1366.
PDB codes: 1ax9 2ack
9914252 W.G.Scott (1998).
RNA catalysis.
  Curr Opin Struct Biol, 8, 720-726.  
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.  
9414203 D.M.van Aalten, D.A.Conn, Groot, H.J.Berendsen, J.B.Findlay, and A.Amadei (1997).
Protein dynamics derived from clusters of crystal structures.
  Biophys J, 73, 2891-2896.  
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.  
9253408 J.E.Murphy, B.Stec, L.Ma, and E.R.Kantrowitz (1997).
Trapping and visualization of a covalent enzyme-phosphate intermediate.
  Nat Struct Biol, 4, 618-622.
PDB code: 1hjk
9345628 K.Moffat, and Z.Ren (1997).
Synchrotron radiation applications to macromolecular crystallography.
  Curr Opin Struct Biol, 7, 689-696.  
9428712 R.Chen, A.F.Greer, and A.M.Dean (1997).
Structural constraints in protein engineering--the coenzyme specificity of Escherichia coli isocitrate dehydrogenase.
  Eur J Biochem, 250, 578-582.  
  8745412 A.M.Dean, A.K.Shiau, and D.E.Koshland (1996).
Determinants of performance in the isocitrate dehydrogenase of Escherichia coli.
  Protein Sci, 5, 341-347.  
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.  
8901863 B.L.Stoddard (1996).
Caught in a chemical trap.
  Nat Struct Biol, 3, 907-909.  
8888067 B.L.Stoddard (1996).
Intermediate trapping and laue X-ray diffraction: potential for enzyme mechanism, dynamics, and inhibitor screening.
  Pharmacol Ther, 70, 215-256.  
8639526 J.H.Hurley, R.Chen, and A.M.Dean (1996).
Determinants of cofactor specificity in isocitrate dehydrogenase: structure of an engineered NADP+ --> NAD+ specificity-reversal mutant.
  Biochemistry, 35, 5670-5678.
PDB code: 1iso
8718877 L.Peng, I.Silman, J.Sussman, and M.Goeldner (1996).
Biochemical evaluation of photolabile precursors of choline and of carbamylcholine for potential time-resolved crystallographic studies on cholinesterases.
  Biochemistry, 35, 10854-10861.  
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.  
8968112 N.E.Chayen, T.J.Boggon, A.Cassetta, A.Deacon, T.Gleichmann, J.Habash, S.J.Harrop, J.R.Helliwell, Y.P.Nieh, M.R.Peterson, J.Raftery, E.H.Snell, A.Hädener, A.C.Niemann, D.P.Siddons, V.Stojanoff, A.W.Thompson, T.Ursby, and M.Wulff (1996).
Trends and challenges in experimental macromolecular crystallography.
  Q Rev Biophys, 29, 227-278.  
8901552 R.Chen, A.Greer, and A.M.Dean (1996).
Redesigning secondary structure to invert coenzyme specificity in isopropylmalate dehydrogenase.
  Proc Natl Acad Sci U S A, 93, 12171-12176.  
  8745407 R.Chen, J.A.Grobler, J.H.Hurley, and A.M.Dean (1996).
Second-site suppression of regulatory phosphorylation in Escherichia coli isocitrate dehydrogenase.
  Protein Sci, 5, 287-295.
PDB codes: 1gro 1grp
8590009 B.L.Stoddard, and G.K.Farber (1995).
Direct measurement of reactivity in the protein crystal by steady-state kinetic studies.
  Structure, 3, 991-996.  
8548273 G.K.Farber (1995).
Laue crystallography. It's show time.
  Curr Biol, 5, 1088-1090.  
7588737 J.Steyaert, and Y.Engelborghs (1995).
A two-binding-site kinetic model for the ribonuclease-T1-catalysed transesterification of dinucleoside phosphate substrates.
  Eur J Biochem, 233, 140-144.  
8574702 K.Moffat, and R.Henderson (1995).
Freeze trapping of reaction intermediates.
  Curr Opin Struct Biol, 5, 656-663.  
8593959 M.L.Camacho, R.A.Brown, M.J.Bonete, M.J.Danson, and D.W.Hough (1995).
Isocitrate dehydrogenases from Haloferax volcanii and Sulfolobus solfataricus: enzyme purification, characterisation and N-terminal sequence.
  FEMS Microbiol Lett, 134, 85-90.  
8749364 T.L.Poulos (1995).
Cytochrome P450.
  Curr Opin Struct Biol, 5, 767-774.  
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