PDBsum entry 4hcx

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
402 a.a.
NDP ×2
_CL ×2
_MN ×2
Waters ×310
PDB id:
Name: Oxidoreductase
Title: Structure of icdh-1 from m.Tuberculosis complexed with nadph
Structure: Isocitrate dehydrogenase [nadp]. Chain: a, b. Synonym: idh, idp, NADP(+)-specific icdh, oxalosuccinate decarboxylase. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: icd, rv3339c, mt3442, mtv016.39c. Expressed in: escherichia coli. Expression_system_taxid: 562
2.18Å     R-factor:   0.205     R-free:   0.262
Authors: S.Hazra,J.Blanchard
Key ref: C.E.Quartararo et al. (2013). Structural, kinetic and chemical mechanism of isocitrate dehydrogenase-1 from Mycobacterium tuberculosis. Biochemistry, 52, 1765-1775. PubMed id: 23409873 DOI: 10.1021/bi400037w
01-Oct-12     Release date:   27-Feb-13    
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Protein chains
P9WKL1  (IDH_MYCTU) -  Isocitrate dehydrogenase [NADP]
409 a.a.
402 a.a.
Key:    Secondary structure  CATH domain

 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 = NDP)
corresponds exactly
= 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!
  Cellular component     plasma membrane   1 term 
  Biological process     oxidation-reduction process   4 terms 
  Biochemical function     protein binding     8 terms  


DOI no: 10.1021/bi400037w Biochemistry 52:1765-1775 (2013)
PubMed id: 23409873  
Structural, kinetic and chemical mechanism of isocitrate dehydrogenase-1 from Mycobacterium tuberculosis.
C.E.Quartararo, S.Hazra, T.Hadi, J.S.Blanchard.
Mycobacterium tuberculosis (Mtb) is the leading cause of death due to a bacterial infection. The success of the Mtb pathogen has largely been attributed to the nonreplicating, persistence phase of the life cycle, for which the glyoxylate shunt is required. In Escherichia coli, flux through the shunt is controlled by regulation of isocitrate dehydrogenase (ICDH). In Mtb, the mechanism of regulation is unknown, and currently, there is no mechanistic or structural information about ICDH. We optimized expression and purification to a yield sufficiently high to perform the first detailed kinetic and structural studies of Mtb ICDH-1. A large solvent kinetic isotope effect [(D2O)V = 3.0 ± 0.2, and (D2O)(V/Kisocitrate) = 1.5 ± 0.3] and a smaller primary kinetic isotope effect [(D)V = 1.3 ± 0.1, and (D)(V/K[2R-(2)H]isocitrate) = 1.5 ± 0.2] allowed us to perform the first multiple kinetic isotope effect studies on any ICDH and suggest a chemical mechanism. In this mechanism, protonation of the enolate to form product α-ketoglutarate is the rate-limiting step. We report the first structure of Mtb ICDH-1 to 2.18 Å by X-ray crystallography with NADPH and Mn(2+) bound. It is a homodimer in which each subunit has a Rossmann fold, and a common top domain of interlocking β sheets. Mtb ICDH-1 is most structurally similar to the R132H mutant human ICDH found in glioblastomas. Similar to human R132H ICDH, Mtb ICDH-1 also catalyzes the formation of α-hydroxyglutarate. Our data suggest that regulation of Mtb ICDH-1 is novel.