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PDBsum entry 2qfw

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
2qfw
Jmol
Contents
Protein chains
(+ 0 more) 407 a.a. *
Ligands
ICT ×6
Waters ×1158
* Residue conservation analysis
PDB id:
2qfw
Name: Oxidoreductase
Title: Crystal structure of saccharomyces cerevesiae mitochondrial dependent isocitrate dehydrogenase in complex with isocitra
Structure: Isocitrate dehydrogenase [nadp]. Chain: a, b, c, d, e, f. Synonym: idp1p, oxalosuccinate decarboxylase, idh, NADP+, - icdh, idp. Engineered: yes
Source: Saccharomyces cerevisiae. Yeast. Organism_taxid: 4932. Strain: yph499. Gene: idp1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.60Å     R-factor:   0.235     R-free:   0.292
Authors: Y.J.Peng,J.P.Ding
Key ref: Y.Peng et al. (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. PubMed id: 18552125
Date:
28-Jun-07     Release date:   01-Jul-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P21954  (IDHP_YEAST) -  Isocitrate dehydrogenase [NADP], mitochondrial
Seq:
Struc:
428 a.a.
407 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
Bound ligand (Het Group name = ICT)
corresponds exactly
+ 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!
  Cellular component     mitochondrion   2 terms 
  Biological process     oxidation-reduction process   5 terms 
  Biochemical function     protein binding     7 terms  

 

 
    reference    
 
 
Protein Sci 17:1542-1554 (2008)
PubMed id: 18552125  
 
 
Structural studies of Saccharomyces cerevesiae mitochondrial NADP-dependent isocitrate dehydrogenase in different enzymatic states reveal substantial conformational changes during the catalytic reaction.
Y.Peng, C.Zhong, W.Huang, J.Ding.
 
  ABSTRACT  
 
Isocitrate dehydrogenases (IDHs) catalyze oxidative decarboxylation of isocitrate (ICT) into alpha-ketoglutarate (AKG). We report here the crystal structures of Saccharomyces cerevesiae mitochondrial NADP-IDH Idp1p in binary complexes with coenzyme NADP, or substrate ICT, or product AKG, and in a quaternary complex with NADPH, AKG, and Ca(2+), which represent different enzymatic states during the catalytic reaction. Analyses of these structures identify key residues involved in the binding of these ligands. Comparisons among these structures and with the previously reported structures of other NADP-IDHs reveal that eukaryotic NADP-IDHs undergo substantial conformational changes during the catalytic reaction. Binding or release of the ligands can cause significant conformational changes of the structural elements composing the active site, leading to rotation of the large domain relative to the small and clasp domains along two hinge regions (residues 118-124 and residues 284-287) while maintaining the integrity of its secondary structural elements, and thus, formation of at least three distinct overall conformations. Specifically, the enzyme adopts an open conformation when bound to NADP, a quasi-closed conformation when bound to ICT or AKG, and a fully closed conformation when bound to NADP, ICT, and Ca(2+) in the pseudo-Michaelis complex or with NADPH, AKG, and Ca(2+) in the product state. The conformational changes of eukaryotic NADP-IDHs are quite different from those of Escherichia coli NADP-IDH, for which significant conformational changes are observed only between two forms of the apo enzyme, suggesting that the catalytic mechanism of eukaryotic NADP-IDHs is more complex than that of EcIDH, and involves more fine-tuned conformational changes.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
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