PDBsum entry 4aov

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Oxidoreductase PDB id
Protein chain
402 a.a.
Waters ×227
PDB id:
Name: Oxidoreductase
Title: Dpidh-NADP. The complex structures of isocitrate dehydrogena clostridium thermocellum and desulfotalea psychrophila, sup new active site locking mechanism
Structure: Isocitrate dehydrogenase [nadp]. Chain: a. Engineered: yes
Source: Desulfotalea psychrophila. Organism_taxid: 84980. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.93Å     R-factor:   0.177     R-free:   0.225
Authors: H.-K.S.Leiros,A.-E.Fedoy,I.Leiros,I.H.Steen
Key ref: H.K.Leiros et al. (2012). The complex structures of isocitrate dehydrogenase from Clostridium thermocellum and Desulfotalea psychrophila suggest a new active site locking mechanism. FEBS Open Bio, 2, 159-172. PubMed id: 23650595 DOI: 10.1016/j.fob.2012.06.003
30-Mar-12     Release date:   11-Jul-12    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q6AQ66  (Q6AQ66_DESPS) -  Isocitrate dehydrogenase [NADP]
402 a.a.
402 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
Bound ligand (Het Group name = ICT)
corresponds exactly
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!
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     nucleotide binding     7 terms  


DOI no: 10.1016/j.fob.2012.06.003 FEBS Open Bio 2:159-172 (2012)
PubMed id: 23650595  
The complex structures of isocitrate dehydrogenase from Clostridium thermocellum and Desulfotalea psychrophila suggest a new active site locking mechanism.
H.K.Leiros, A.E.Fedøy, I.Leiros, I.H.Steen.
Isocitrate dehydrogenase (IDH) catalyzes the oxidative NAD(P)(+)-dependent decarboxylation of isocitrate into α-ketoglutarate and CO2 and is present in organisms spanning the biological range of temperature. We have solved two crystal structures of the thermophilic Clostridium thermocellum IDH (CtIDH), a native open apo CtIDH to 2.35 Å and a quaternary complex of CtIDH with NADP(+), isocitrate and Mg(2+) to 2.5 Å. To compare to these a quaternary complex structure of the psychrophilic Desulfotalea psychrophila IDH (DpIDH) was also resolved to 1.93 Å. CtIDH and DpIDH showed similar global thermal stabilities with melting temperatures of 67.9 and 66.9 °C, respectively. CtIDH represents a typical thermophilic enzyme, with a large number of ionic interactions and hydrogen bonds per residue combined with stabilization of the N and C termini. CtIDH had a higher activity temperature optimum, and showed greater affinity for the substrates with an active site that was less thermolabile compared to DpIDH. The uncompensated negative surface charge and the enlarged methionine cluster in the hinge region both of which are important for cold activity in DpIDH, were absent in CtIDH. These structural comparisons revealed that prokaryotic IDHs in subfamily II have a unique locking mechanism involving Arg310, Asp251' and Arg255 (CtIDH). These interactions lock the large domain to the small domain and direct NADP(+) into the correct orientation, which together are important for NADP(+) selectivity.