PDBsum entry 4aj3

Go to PDB code: 
protein ligands metals links
Oxidoreductase PDB id
Protein chain
416 a.a.
Waters ×374
PDB id:
Name: Oxidoreductase
Title: 3d structure of e. Coli isocitrate dehydrogenase in complex isocitrate, calcium(ii) and NADP - the pseudo-michaelis com
Structure: NADP isocitrate dehydrogenase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 83333. Strain: k-12. Expressed in: escherichia coli. Expression_system_taxid: 562
1.90Å     R-factor:   0.190     R-free:   0.224
Authors: S.Goncalves,S.P.Miller,M.A.Carrondo,A.M.Dean,P.M.Matias
Key ref: S.Gonçalves et al. (2012). Induced fit and the catalytic mechanism of isocitrate dehydrogenase. Biochemistry, 51, 7098-7115. PubMed id: 22891681 DOI: 10.1021/bi300483w
15-Feb-12     Release date:   31-Oct-12    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08200  (IDH_ECOLI) -  Isocitrate dehydrogenase [NADP]
416 a.a.
416 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     oxidation-reduction process   5 terms 
  Biochemical function     oxidoreductase activity     6 terms  


DOI no: 10.1021/bi300483w Biochemistry 51:7098-7115 (2012)
PubMed id: 22891681  
Induced fit and the catalytic mechanism of isocitrate dehydrogenase.
S.Gonçalves, S.P.Miller, M.A.Carrondo, A.M.Dean, P.M.Matias.
NADP(+) dependent isocitrate dehydrogenase (IDH; EC belongs to a large family of α-hydroxyacid oxidative β-decarboxylases that catalyze similar three-step reactions, with dehydrogenation to an oxaloacid intermediate preceding β-decarboxylation to an enol intermediate followed by tautomerization to the final α-ketone product. A comprehensive view of the induced fit needed for catalysis is revealed on comparing the first "fully closed" crystal structures of a pseudo-Michaelis complex of wild-type Escherichia coli IDH (EcoIDH) and the "fully closed" reaction product complex of the K100M mutant with previously obtained "quasi-closed" and "open" conformations. Conserved catalytic residues, binding the nicotinamide ring of NADP(+) and the metal-bound substrate, move as rigid bodies during domain closure by a hinge motion that spans the central β-sheet in each monomer. Interactions established between Thr105 and Ser113, which flank the "phosphorylation loop", and the nicotinamide mononucleotide moiety of NADP(+) establish productive coenzyme binding. Electrostatic interactions of a Lys100-Leu103-Asn115-Glu336 tetrad play a pivotal role in assembling a catalytically competent active site. As predicted, Lys230* is positioned to deprotonate/reprotonate the α-hydroxyl in both reaction steps and Tyr160 moves into position to protonate C3 following β-decarboxylation. A proton relay from the catalytic triad Tyr160-Asp307-Lys230* connects the α-hydroxyl of isocitrate to the bulk solvent to complete the picture of the catalytic mechanism.