PDBsum entry 1hqs

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Oxidoreductase PDB id
Protein chains
423 a.a. *
CIT ×2
PGO ×5
PGR ×2
Waters ×608
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of isocitrate dehydrogenase from bacillus subtilis
Structure: Isocitrate dehydrogenase. Chain: a, b. Synonym: oxalosuccinate decarboxylase. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Gene: citc. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
1.55Å     R-factor:   0.202     R-free:   0.249
Authors: S.K.Singh,K.Matsuno,D.C.Laporte,L.J.Banaszak
Key ref:
S.K.Singh et al. (2001). Crystal structure of Bacillus subtilis isocitrate dehydrogenase at 1.55 A. Insights into the nature of substrate specificity exhibited by Escherichia coli isocitrate dehydrogenase kinase/phosphatase. J Biol Chem, 276, 26154-26163. PubMed id: 11290745 DOI: 10.1074/jbc.M101191200
19-Dec-00     Release date:   25-Jul-01    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P39126  (IDH_BACSU) -  Isocitrate dehydrogenase [NADP]
423 a.a.
423 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 = CIT)
matches with 85.00% similarity
+ 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!
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     protein binding     7 terms  


DOI no: 10.1074/jbc.M101191200 J Biol Chem 276:26154-26163 (2001)
PubMed id: 11290745  
Crystal structure of Bacillus subtilis isocitrate dehydrogenase at 1.55 A. Insights into the nature of substrate specificity exhibited by Escherichia coli isocitrate dehydrogenase kinase/phosphatase.
S.K.Singh, K.Matsuno, D.C.LaPorte, L.J.Banaszak.
Isocitrate dehydrogenase from Bacillus subtilis (BsIDH) is a member of a family of metal-dependent decarboxylating dehydrogenases. Its crystal structure was solved to 1.55 A and detailed comparisons with the homologue from Escherichia coli (EcIDH), the founding member of this family, were made. Although the two IDHs are structurally similar, there are three notable differences between them. First, a mostly nonpolar beta-strand and two connecting loops in the small domain of EcIDH are replaced by two polar alpha-helices in BsIDH. Because of a 13-residue insert in this region of BsIDH, these helices protrude over the active site cleft of the opposing monomer. Second, a coil leading into this cleft, the so-called "phosphorylation" loop, is bent inward in the B. subtilis enzyme, narrowing the entrance to the active site from about 12 to 4 A. Third, although BsIDH is a homodimer, the two unique crystallographic subunits of BsIDH are not structurally identical. The two monomers appear to differ by a domain shift of the large domain relative to the small domain/clasp region, reminiscent of what has been observed in the open/closed conformations of EcIDH. In Escherichia coli, IDH is regulated by reversible phosphorylation by the bifunctional enzyme IDH kinase/phosphatase (IDH-K/P). The site of phosphorylation is Ser(113), which lies deep within the active site crevice. Structural differences between EcIDH and BsIDH may explain disparities in their abilities to act as substrates for IDH-K/P.
  Selected figure(s)  
Figure 6.
Fig. 6. The phosphorylation loop is disordered in only one monomer of BsIDH. 2| F[o]| |F[c]| electron density maps, contoured at 1 , of a majority of the phosphorylation loop in BsIDH. A, the loop in monomer A, illustrating the unequivocal position of the constituent amino acids; B, the loop in monomer B, depicting the ambiguous location, perhaps increased mobility, of the same residues. Atoms are shaded as follows: light gray (carbon), dark gray (oxygen), and black (nitrogen).
Figure 7.
Fig. 7. Accessibility of the phosphorylation site in BsIDH and EcIDH. A, global overlay of the two IDHs. BsIDH is light green and EcIDH is blue. The phosphorylated serine (Ser104 in BsIDH, Ser113 in EcIDH) is red. B, magnification of the insert region and active site with relevant side chains added. Labels of selected residues in BsIDH are black; those in EcIDH are reddish-gray. The phosphorylated serine is red and is clearly occluded. Indicated amino acids in the insert region of BsIDH include 242EKEYGDKVFTWAQYDRIAEEQGKDAANKAQSEAEAAGK278. Indicated residues in this area of EcIDH include 251REEFGGELIDGGPWLKVKNPNTGKE^271. Although there is little structural homology between the two IDHs in the insert region, there is a small stretch of -strand that overlaps. The segment in BsIDH includes 247KVFTWA^252 and that in EcIDH includes 267KVKLWP262, and, as suggested by the numbering, they run in opposite directions. Note that residue 259 in EcIDH (not labeled) is supposed to be an aspartate, but according to the header from PDB code 5ICD, this amino acid was truncated at the -carbon because some "side chain atoms could not be located in the electron density maps". C, molecular surface rendering of the active site, phosphorylation loop, and insert region (lack thereof) in phosphorylated EcIDH (6; PDB code 4ICD); recall that there is no dramatic conformational change between the dephosphorylated and phosphorylated forms of EcIDH. One monomer is cyan; the other is white. The phosphate moiety on Ser113 is red/white and is depicted as a van der Waals surface. D, molecular surface rendering of the corresponding segments in BsIDH. The subunits and modeled phosphate moiety on Ser104 are colored as they are in C. The phosphate is obscured both by the large indentation of the phosphorylation loop and the insert region of the opposing monomer. For clarity, the view represented in A and B has been rotated slightly toward the reader relative to that presented in C and D. Panels C and D were generated with GRASP (46).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2001, 276, 26154-26163) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20505668 J.Zheng, and Z.Jia (2010).
Structure of the bifunctional isocitrate dehydrogenase kinase/phosphatase.
  Nature, 465, 961-965.
PDB codes: 3eps 3lc6 3lcb
20376324 N.Zhang, A.Gur, Y.Gibon, R.Sulpice, S.Flint-Garcia, M.D.McMullen, M.Stitt, and E.S.Buckler (2010).
Genetic analysis of central carbon metabolism unveils an amino acid substitution that alters maize NAD-dependent isocitrate dehydrogenase activity.
  PLoS One, 5, e9991.  
18723842 J.Zhang, R.Sprung, J.Pei, X.Tan, S.Kim, H.Zhu, C.F.Liu, N.V.Grishin, and Y.Zhao (2009).
Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli.
  Mol Cell Proteomics, 8, 215-225.  
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
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
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.  
15686840 H.Iwabata, K.Watanabe, T.Ohkuri, S.Yokobori, and A.Yamagishi (2005).
Thermostability of ancestral mutants of Caldococcus noboribetus isocitrate dehydrogenase.
  FEMS Microbiol Lett, 243, 393-398.  
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.  
15146507 J.J.Jeong, T.Sonoda, S.Fushinobu, H.Shoun, and T.Wakagi (2004).
Crystal structure of isocitrate dehydrogenase from Aeropyrum pernix.
  Proteins, 55, 1087-1089.
PDB code: 1v94
15062079 P.P.Iyer, S.H.Lawrence, K.B.Luther, K.R.Rajashankar, H.P.Yennawar, J.G.Ferry, and H.Schindelin (2004).
Crystal structure of phosphotransacetylase from the methanogenic archaeon Methanosarcina thermophila.
  Structure, 12, 559-567.
PDB code: 1qzt
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.  
12007799 M.Camacho, A.Rodríguez-Arnedo, and M.J.Bonete (2002).
NADP-dependent isocitrate dehydrogenase from the halophilic archaeon Haloferax volcanii: cloning, sequence determination and overexpression in Escherichia coli.
  FEMS Microbiol Lett, 209, 155-160.  
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.