PDBsum entry 2d4v

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
Jmol PyMol
Protein chains
427 a.a. *
FLC ×4
NAD ×4
Waters ×1333
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of NAD dependent isocitrate dehydrogenase from acidithiobacillus thiooxidans
Structure: Isocitrate dehydrogenase. Chain: a, b, c, d. Engineered: yes
Source: Acidithiobacillus thiooxidans. Organism_taxid: 930. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
1.90Å     R-factor:   0.181     R-free:   0.203
Authors: K.Imada,T.Tamura,K.Namba,K.Inagaki
Key ref:
K.Imada et al. (2008). Structure and quantum chemical analysis of NAD+-dependent isocitrate dehydrogenase: hydride transfer and co-factor specificity. Proteins, 70, 63-71. PubMed id: 17634983 DOI: 10.1002/prot.21486
24-Oct-05     Release date:   14-Nov-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q8GAX0  (Q8GAX0_THITH) -  Isocitrate dehydrogenase
429 a.a.
427 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     nucleotide binding     4 terms  


DOI no: 10.1002/prot.21486 Proteins 70:63-71 (2008)
PubMed id: 17634983  
Structure and quantum chemical analysis of NAD+-dependent isocitrate dehydrogenase: hydride transfer and co-factor specificity.
K.Imada, T.Tamura, R.Takenaka, I.Kobayashi, K.Namba, K.Inagaki.
The crystal structure of Acidithiobacillus thiooxidans isocitrate dehydrogenase complexed with NAD+ and citrate has been solved to a resolution of 1.9 A. The protein fold of this NAD+-dependent enzyme shares a high similarity with those of NADP+-dependent bacterial ICDHs. The NAD+ and the citrate are clearly identified in the active site cleft with a well-defined electron density. Asp-357 is the direct cofactor-specificity determinant that interacts with 2'-OH and 3'-OH of the adenosine ribose. The adenosine ribose takes a C2'-endo puckering conformation as previously reported for an NAD+-specific isopropylmalate dehydrogenase. The nicotinamide moiety of NAD+ has the amide NH2 group oriented in cis conformation with respect to the C4 carbon of the nicotinamide ring, slanted toward the bound citrate molecule with a dihedral angle of -21 degrees . The semi-empirical molecular orbital calculation suggests that the pro-R hydrogen atom at C4 of NADH would bear the largest negative charge when the amide NH2 group is in such conformation, suggesting that the amide group has a catalytically significant role in stabilizing the transition state as NADH is being formed during the hydride transfer catalysis.
  Selected figure(s)  
Figure 4.
Figure 4. Stereo view of the refined structure around the bound NAD^+. The D-i loop of At-ICDH interacting with nicotinamide and adenosine rings simultaneously. The citrate and NAD^+ are shown with brown and green bonds, respectively. Residues in the D-i loop are colored pink and other residues involved in the interaction to NAD^+ are colored cyan. Residues forming the adenine-binding pocket are indicated as ball-and-stick models. Yellow dotted lines indicate hydrogen bonds. W69 is a water molecule.
Figure 6.
Figure 6. MOPAC calculation of electrostatic potentials of hydrogens on the nicotinamide ring. Electrostatic potentials of hydrogens in the reduced form of the nicotinamide ring are calculated at the MNDO,[28] AM1,[29] and PM3[30] levels as a function of the dihedral angle ( [am]). The electrostatic potentials of pro-R and pro-S hydrogens are plotted with solid circles in green and magenta, respectively. The potentials for hydrogen atoms on C5, C6, and C2 are indicated by open and closed squares, and open triangle, respectively. The dihedral angle [am] = -21° elucidated for the enzyme-bound NAD^+ corresponds to the electrostatic conditions in which the pro-R hydrogen of NADH is allowed to bear the most prominent negative charge.
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 70, 63-71) copyright 2008.  
  Figures were selected by the author.