spacer
spacer

PDBsum entry 4aj3

Go to PDB code: 
protein ligands metals links
Oxidoreductase PDB id
4aj3
Jmol
Contents
Protein chain
416 a.a.
Ligands
NAP
ICT
Metals
_CA
Waters ×374
PDB id:
4aj3
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
Resolution:
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
Date:
15-Feb-12     Release date:   31-Oct-12    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P08200  (IDH_ECOLI) -  Isocitrate dehydrogenase [NADP]
Seq:
Struc:
416 a.a.
416 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(+)
Bound ligand (Het Group name = NAP)
corresponds exactly
= 2-oxoglutarate
+ CO(2)
+ NADPH
      Cofactor: Manganese or magnesium
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   5 terms 
  Biochemical function     oxidoreductase activity     6 terms  

 

 
    reference    
 
 
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.
 
  ABSTRACT  
 
NADP(+) dependent isocitrate dehydrogenase (IDH; EC 1.1.1.42) 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.