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PDBsum entry 1itw

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
1itw
Jmol
Contents
Protein chains
740 a.a. *
Ligands
ICT ×4
Metals
_MN ×5
Waters ×2306
* Residue conservation analysis
PDB id:
1itw
Name: Oxidoreductase
Title: Crystal structure of the monomeric isocitrate dehydrogenase in complex with isocitrate and mn
Structure: Isocitrate dehydrogenase. Chain: a, b, c, d. Ec: 1.1.1.42
Source: Azotobacter vinelandii. Organism_taxid: 354. Strain: iam1078
Resolution:
1.95Å     R-factor:   0.193     R-free:   0.228
Authors: Y.Yasutake,S.Watanabe,M.Yao,Y.Takada,N.Fukunaga,I.Tanaka
Key ref:
Y.Yasutake et al. (2002). Structure of the monomeric isocitrate dehydrogenase: evidence of a protein monomerization by a domain duplication. Structure, 10, 1637-1648. PubMed id: 12467571 DOI: 10.1016/S0969-2126(02)00904-8
Date:
12-Feb-02     Release date:   11-Dec-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P16100  (IDH_AZOVI) -  Isocitrate dehydrogenase [NADP]
Seq:
Struc:
 
Seq:
Struc:
741 a.a.
740 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.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     cytoplasm   1 term 
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     oxidoreductase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(02)00904-8 Structure 10:1637-1648 (2002)
PubMed id: 12467571  
 
 
Structure of the monomeric isocitrate dehydrogenase: evidence of a protein monomerization by a domain duplication.
Y.Yasutake, S.Watanabe, M.Yao, Y.Takada, N.Fukunaga, I.Tanaka.
 
  ABSTRACT  
 
NADP(+)-dependent isocitrate dehydrogenase is a member of the beta-decarboxylating dehydrogenase family and catalyzes the oxidative decarboxylation reaction from 2R,3S-isocitrate to yield 2-oxoglutarate and CO(2) in the Krebs cycle. Although most prokaryotic NADP(+)-dependent isocitrate dehydrogenases (IDHs) are homodimeric enzymes, the monomeric IDH with a molecular weight of 80-100 kDa has been found in a few species of bacteria. The 1.95 A crystal structure of the monomeric IDH revealed that it consists of two distinct domains, and its folding topology is related to the dimeric IDH. The structure of the large domain repeats a motif observed in the dimeric IDH. Such a fusional structure by domain duplication enables a single polypeptide chain to form a structure at the catalytic site that is homologous to the dimeric IDH, the catalytic site of which is located at the interface of two identical subunits.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Structural Comparison between Substrate and Metal Ion Binding Sites of the Monomeric and Dimeric IDHs(A) Stereo view of the substrate and metal ion binding site of the monomeric IDH from A. vinelandii. The isocitrate and Mn2+ binding residues of the monomeric IDH, red; the isocitrate molecule, magenta; Mn2+, blue.(B) Stereo view of the substrate and metal ion binding site of the dimeric IDH from E. coli. The isocitrate and Mg2+ binding residues of the dimeric IDH, red; the isocitrate molecule, magenta; Mg2+, blue. Two residues (Lys230' and Asp283') belong to another subunit. The residues that construct the substrate and metal ion binding sites are completely identical between the monomeric and dimeric IDHs.
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 1637-1648) copyright 2002.  
  Figure was selected by an automated process.  

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
  19052369 G.N.Hatzopoulos, G.Kefala, and J.Mueller-Dieckmann (2008).
Cloning, expression, purification, crystallization and preliminary X-ray crystallographic analysis of isocitrate dehydrogenase 2 (Rv0066c) from Mycobacterium tuberculosis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1139-1142.  
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
16416443 F.Imabayashi, S.Aich, L.Prasad, and L.T.Delbaere (2006).
Substrate-free structure of a monomeric NADP isocitrate dehydrogenase: an open conformation phylogenetic relationship of isocitrate dehydrogenase.
  Proteins, 63, 100-112.
PDB code: 2b0t
16418792 S.Maki, M.Yoneta, and Y.Takada (2006).
Two isocitrate dehydrogenases from a psychrophilic bacterium, Colwellia psychrerythraea.
  Extremophiles, 10, 237-249.  
15576556 T.K.Kim, and R.F.Colman (2005).
Ser95, Asn97, and Thr78 are important for the catalytic function of porcine NADP-dependent isocitrate dehydrogenase.
  Protein Sci, 14, 140-147.  
  16511117 V.Oganesyan, C.Huang, P.D.Adams, J.Jancarik, H.A.Yokota, R.Kim, and S.H.Kim (2005).
Structure of a NAD kinase from Thermotoga maritima at 2.3 A resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 640-646.
PDB code: 1yt5
15048835 R.Das, and M.Gerstein (2004).
A method using active-site sequence conservation to find functional shifts in protein families: application to the enzymes of central metabolism, leading to the identification of an anomalous isocitrate dehydrogenase in pathogens.
  Proteins, 55, 455-463.  
15598351 S.Cheek, Y.Qi, S.S.Krishna, L.N.Kinch, and N.V.Grishin (2004).
4SCOPmap: automated assignment of protein structures to evolutionary superfamilies.
  BMC Bioinformatics, 5, 197.  
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
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.