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PDBsum entry 1xgv

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protein Protein-protein interface(s) links
Oxidoreductase PDB id
1xgv
Jmol
Contents
Protein chains
430 a.a. *
Waters ×162
* Residue conservation analysis
PDB id:
1xgv
Name: Oxidoreductase
Title: Isocitrate dehydrogenase from the hyperthermophile aeropyrum
Structure: Isocitrate dehydrogenase. Chain: a, b. Engineered: yes
Source: Aeropyrum pernix. Organism_taxid: 56636. Gene: baa79665. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.20Å     R-factor:   0.226     R-free:   0.251
Authors: M.Karlstrom,R.Stokke,I.H.Steen,N.-K.Birkeland,R.Ladenstein
Key ref:
M.Karlström et al. (2005). Isocitrate dehydrogenase from the hyperthermophile Aeropyrum pernix: X-ray structure analysis of a ternary enzyme-substrate complex and thermal stability. J Mol Biol, 345, 559-577. PubMed id: 15581899 DOI: 10.1016/j.jmb.2004.10.025
Date:
17-Sep-04     Release date:   20-Sep-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9YE81  (Q9YE81_AERPE) -  Isocitrate dehydrogenase [NADP]
Seq:
Struc:
432 a.a.
430 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.42  - Isocitrate dehydrogenase (NADP(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Citric acid cycle
      Reaction: Isocitrate + NADP+ = 2-oxoglutarate + CO2 + NADPH
Isocitrate
+ NADP(+)
= 2-oxoglutarate
+ CO(2)
+ NADPH
      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   1 term 
  Biochemical function     nucleotide binding     6 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2004.10.025 J Mol Biol 345:559-577 (2005)
PubMed id: 15581899  
 
 
Isocitrate dehydrogenase from the hyperthermophile Aeropyrum pernix: X-ray structure analysis of a ternary enzyme-substrate complex and thermal stability.
M.Karlström, R.Stokke, I.H.Steen, N.K.Birkeland, R.Ladenstein.
 
  ABSTRACT  
 
Isocitrate dehydrogenase from Aeropyrum pernix (ApIDH) is a homodimeric enzyme that belongs to the beta-decarboxylating dehydrogenase family and is the most thermostable IDH identified. It catalyzes the NADP+ and metal-dependent oxidative decarboxylation of isocitrate to alpha-ketoglutarate. We have solved the crystal structures of a native ApIDH at 2.2 A, a pseudo-native ApIDH at 2.1 A, and of ApIDH in complex with NADP+, Ca2+ and d-isocitrate at 2.3 A. The pseudo-native ApIDH is in complex with etheno-NADP+ which was located at the surface instead of in the active site revealing a novel adenine-nucleotide binding site in ApIDH. The native and the pseudo-native ApIDHs were found in an open conformation, whereas one of the subunits of the ternary complex was closed upon substrate binding. The closed subunit showed a domain rotation of 19 degrees compared to the open subunit. The binding of isocitrate in the closed subunit was identical with that of the binary complex of porcine mitochondrial IDH, whereas the binding of NADP+ was similar to that of the ternary complex of IDH from Escherichiacoli. The reaction mechanism is likely to be conserved in the different IDHs. A proton relay chain involving at least five solvent molecules, the 5'-phosphate group of the nicotinamide-ribose and a coupled lysine-tyrosine pair in the active site, is postulated as essential in both the initial and the final steps of the catalytic reaction of IDH. ApIDH was found to be highly homologous to the mesophilic IDHs and was subjected to a comparative analysis in order to find differences that could explain the large difference in thermostability. Mutational studies revealed that a disulfide bond at the N terminus and a seven-membered inter-domain ionic network at the surface are major determinants for the higher thermostability of ApIDH compared to EcIDH. Furthermore, the total number of ion pairs was dramatically higher in ApIDH compared to the mesophilic IDHs if a cutoff of 4.2 A was used. A calculated net charge of only +1 compared to -19 and -25 in EcIDH and BsIDH, respectively, suggested a high degree of electrostatic optimization, which is known to be an important determinant for increased thermostability.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Overlay of native ApIDH (grey) and the open form of E. coli IDH (blue, PDB code 1SJS) and of the closed subunit of the ternary complex of ApIDH (green) and B. subtilis IDH (red, PDB code 1HQS).
Figure 5.
Figure 5. Coordination of Ca 2C in subunit A (a) and B (b) of the ternary complex of ApIDH. In subunit A, Ca 2C has eight ligands. The water y3 and Asp315 are 2.6 Å and 2.4 Å away, respectively. In subunit B, Ca 2C has six ligands, the water corresponding to y3 is absent and Asp315 has moved by 1.3 Å to 3.7 Å from Ca 2C .
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 345, 559-577) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20483913 A.Guelorget, M.Roovers, V.Guérineau, C.Barbey, X.Li, and B.Golinelli-Pimpaneau (2010).
Insights into the hyperthermostability and unusual region-specificity of archaeal Pyrococcus abyssi tRNA m1A57/58 methyltransferase.
  Nucleic Acids Res, 38, 6206-6218.
PDB codes: 3lga 3lhd 3mb5
20975740 B.Yang, C.Zhong, Y.Peng, Z.Lai, and J.Ding (2010).
Molecular mechanisms of "off-on switch" of activities of human IDH1 by tumor-associated mutation R132H.
  Cell Res, 20, 1188-1200.
PDB codes: 3map 3mar 3mas
20058042 M.Karlström, R.Chiaraluce, L.Giangiacomo, I.H.Steen, N.K.Birkeland, R.Ladenstein, and V.Consalvi (2010).
Thermodynamic and kinetic stability of a large multi-domain enzyme from the hyperthermophile Aeropyrum pernix.
  Extremophiles, 14, 213-223.  
20516620 R.Malik, and R.E.Viola (2010).
Structural characterization of tartrate dehydrogenase: a versatile enzyme catalyzing multiple reactions.
  Acta Crystallogr D Biol Crystallogr, 66, 673-684.
PDB codes: 3flk 3fmx
18513746 N.P.King, T.M.Lee, M.R.Sawaya, D.Cascio, and T.O.Yeates (2008).
Structures and functional implications of an AMP-binding cystathionine beta-synthase domain protein from a hyperthermophilic archaeon.
  J Mol Biol, 380, 181-192.
PDB codes: 2rif 2rih
17508126 R.Ladenstein, and B.Ren (2008).
Reconsideration of an early dogma, saying "there is no evidence for disulfide bonds in proteins from archaea".
  Extremophiles, 12, 29-38.  
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
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
18073113 M.Kuratani, Y.Yoshikawa, Y.Bessho, K.Higashijima, T.Ishii, R.Shibata, S.Takahashi, K.Yutani, and S.Yokoyama (2007).
Structural basis of the initial binding of tRNA(Ile) lysidine synthetase TilS with ATP and L-lysine.
  Structure, 15, 1642-1653.
PDB codes: 2e21 2e89
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
17123127 R.Stokke, N.K.Birkeland, and I.H.Steen (2007).
Thermal stability and biochemical properties of isocitrate dehydrogenase from the thermoacidophilic archaeon Thermoplasma acidophilum.
  Extremophiles, 11, 397-402.  
16759231 M.Karlström, I.H.Steen, D.Madern, A.E.Fedöy, N.K.Birkeland, and R.Ladenstein (2006).
The crystal structure of a hyperthermostable subfamily II isocitrate dehydrogenase from Thermotoga maritima.
  FEBS J, 273, 2851-2868.
PDB code: 1zor
16930136 R.Ladenstein, and B.Ren (2006).
Protein disulfides and protein disulfide oxidoreductases in hyperthermophiles.
  FEBS J, 273, 4170-4185.  
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.  
16166541 J.Miyazaki, K.Asada, S.Fushinobu, T.Kuzuyama, and M.Nishiyama (2005).
Crystal structure of tetrameric homoisocitrate dehydrogenase from an extreme thermophile, Thermus thermophilus: involvement of hydrophobic dimer-dimer interaction in extremely high thermotolerance.
  J Bacteriol, 187, 6779-6788.
PDB code: 1x0l
16111437 M.Beeby, B.D.O'Connor, C.Ryttersgaard, D.R.Boutz, L.J.Perry, and T.O.Yeates (2005).
The genomics of disulfide bonding and protein stabilization in thermophiles.
  PLoS Biol, 3, e309.
PDB code: 1rki
15975917 Y.C.Huang, and R.F.Colman (2005).
Location of the coenzyme binding site in the porcine mitochondrial NADP-dependent isocitrate dehydrogenase.
  J Biol Chem, 280, 30349-30353.  
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.