PDBsum entry 1nfs

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Isomerase PDB id
Protein chains
176 a.a. *
DED ×2
_MN ×2
_MG ×2
Waters ×117
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Structure and mechanism of action of isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase: complex with nipp
Structure: Isopentenyl-diphosphate delta-isomerase. Chain: a, b. Synonym: dimethylallyl diphosphate isomerase, ipp isomerase, isopentenyl pyrophosphate isomerase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
1.96Å     R-factor:   0.222     R-free:   0.260
Authors: J.Wouters
Key ref:
J.Wouters et al. (2003). Catalytic mechanism of Escherichia coli isopentenyl diphosphate isomerase involves Cys-67, Glu-116, and Tyr-104 as suggested by crystal structures of complexes with transition state analogues and irreversible inhibitors. J Biol Chem, 278, 11903-11908. PubMed id: 12540835 DOI: 10.1074/jbc.M212823200
16-Dec-02     Release date:   24-Jun-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q46822  (IDI_ECOLI) -  Isopentenyl-diphosphate Delta-isomerase
182 a.a.
176 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Isopentenyl-diphosphate Delta-isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Terpenoid biosynthesis
      Reaction: Isopentenyl diphosphate = dimethylallyl diphosphate
Isopentenyl diphosphate
Bound ligand (Het Group name = DED)
matches with 64.00% similarity
= dimethylallyl diphosphate
      Cofactor: FAD or FMN; Mg(2+) or Ca(2+) or Mn(2+)
or FMN
or Ca(2+)
or Mn(2+)
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     response to DNA damage stimulus   4 terms 
  Biochemical function     hydrolase activity     4 terms  


DOI no: 10.1074/jbc.M212823200 J Biol Chem 278:11903-11908 (2003)
PubMed id: 12540835  
Catalytic mechanism of Escherichia coli isopentenyl diphosphate isomerase involves Cys-67, Glu-116, and Tyr-104 as suggested by crystal structures of complexes with transition state analogues and irreversible inhibitors.
J.Wouters, Y.Oudjama, S.J.Barkley, C.Tricot, V.Stalon, L.Droogmans, C.D.Poulter.
Isopentenyl diphosphate (IPP):dimethylallyl diphosphate (DMAPP) isomerase is a key enzyme in the biosynthesis of isoprenoids. The reaction involves protonation and deprotonation of the isoprenoid unit and proceeds through a carbocationic transition state. Analysis of the crystal structures (2 A) of complexes of Escherichia coli IPP.DMAPPs isomerase with a transition state analogue (N,N-dimethyl-2-amino-1-ethyl diphosphate) and a covalently attached irreversible inhibitor (3,4-epoxy-3-methyl-1-butyl diphosphate) indicates that Glu-116, Tyr-104, and Cys-67 are involved in the antarafacial addition/elimination of protons during isomerization. This work provides a new perspective about the mechanism of the reaction.
  Selected figure(s)  
Figure 3.
Fig. 3. View of the binding site of wild-type IPP isomerase in complex with NIPP (a) and EIPP (b).
Figure 4.
Fig. 4. Proposed mechanism for isomerization of IPP to DMAPP based on the structures of complexes with NIPP and EIPP. Evidence from the crystal structures of complexes with NIPP and EIPP strongly points to Tyr-104 being the proton donor. Glu-116 is likely the critical acidic residue that drives protonation by lowering the energy of the carbocation.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 11903-11908) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18793870 H.Eoh, P.J.Brennan, and D.C.Crick (2009).
The Mycobacterium tuberculosis MEP (2C-methyl-d-erythritol 4-phosphate) pathway as a new drug target.
  Tuberculosis (Edinb), 89, 1.  
18655062 A.Liavonchanka, and I.Feussner (2008).
Biochemistry of PUFA double bond isomerases producing conjugated linoleic acid.
  Chembiochem, 9, 1867-1872.  
  18391416 Ruyck, Y.Oudjama, and J.Wouters (2008).
Monoclinic form of isopentenyl diphosphate isomerase: a case of polymorphism in biomolecular crystals.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 239-242.
PDB codes: 2vnp 2vnq
17606904 J.A.Maresca, J.E.Graham, M.Wu, J.A.Eisen, and D.A.Bryant (2007).
Identification of a fourth family of lycopene cyclases in photosynthetic bacteria.
  Proc Natl Acad Sci U S A, 104, 11784-11789.  
17428035 S.C.Rothman, T.R.Helm, and C.D.Poulter (2007).
Kinetic and spectroscopic characterization of type II isopentenyl diphosphate isomerase from Thermus thermophilus: evidence for formation of substrate-induced flavin species.
  Biochemistry, 46, 5437-5445.  
17928693 T.Hoshino, and T.Eguchi (2007).
Functional analysis of type 1 isopentenyl diphosphate isomerase from Halobacterium sp. NRC-1.
  Biosci Biotechnol Biochem, 71, 2588-2591.  
16793276 T.Hoshino, H.Tamegai, K.Kakinuma, and T.Eguchi (2006).
Inhibition of type 2 isopentenyl diphosphate isomerase from Methanocaldococcus jannaschii by a mechanism-based inhibitor of type 1 isopentenyl diphosphate isomerase.
  Bioorg Med Chem, 14, 6555-6559.  
16289312 F.Bouvier, A.Rahier, and B.Camara (2005).
Biogenesis, molecular regulation and function of plant isoprenoids.
  Prog Lipid Res, 44, 357-429.  
15765206 J.Yochem, D.H.Hall, L.R.Bell, E.M.Hedgecock, and R.K.Herman (2005).
Isopentenyl-diphosphate isomerase is essential for viability of Caenorhabditis elegans.
  Mol Genet Genomics, 273, 158-166.  
16332094 Z.Wu, J.Wouters, and C.D.Poulter (2005).
Isopentenyl diphosphate isomerase. Mechanism-based inhibition by diene analogues of isopentenyl diphosphate and dimethylallyl diphosphate.
  J Am Chem Soc, 127, 17433-17438.  
15162484 G.W.Buchko, S.Ni, S.R.Holbrook, and M.A.Kennedy (2004).
Solution structure of hypothetical Nudix hydrolase DR0079 from extremely radiation-resistant Deinococcus radiodurans bacterium.
  Proteins, 56, 28-39.
PDB code: 1q27
14696183 J.Wouters, Y.Oudjama, V.Stalon, L.Droogmans, and C.D.Poulter (2004).
Crystal structure of the C67A mutant of isopentenyl diphosphate isomerase complexed with a mechanism-based irreversible inhibitor.
  Proteins, 54, 216-221.
PDB code: 1ow2
15206931 R.Laupitz, S.Hecht, S.Amslinger, F.Zepeck, J.Kaiser, G.Richter, N.Schramek, S.Steinbacher, R.Huber, D.Arigoni, A.Bacher, W.Eisenreich, and F.Rohdich (2004).
Biochemical characterization of Bacillus subtilis type II isopentenyl diphosphate isomerase, and phylogenetic distribution of isoprenoid biosynthesis pathways.
  Eur J Biochem, 271, 2658-2669.  
14996812 S.J.Barkley, R.M.Cornish, and C.D.Poulter (2004).
Identification of an Archaeal type II isopentenyl diphosphate isomerase in methanothermobacter thermautotrophicus.
  J Bacteriol, 186, 1811-1817.  
15547291 S.J.Barkley, S.B.Desai, and C.D.Poulter (2004).
Type II isopentenyl diphosphate isomerase from Synechocystis sp. strain PCC 6803.
  J Bacteriol, 186, 8156-8158.  
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.