Isopentenyl-diphosphate delta isomerase

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isopentenyl-diphosphate Δ-isomerase
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Isopentenyl-pyrophosphate Δ isomerase 1
Identifiers
SymbolIDI1
Chr. 10 p15.3
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StructuresSwiss-model
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Isopentenyl pyrophosphate isomerase (

MEP pathway
.

isopentenyl diphosphate dimethylallyl diphosphate

This enzyme belongs to the family of isomerases, specifically those intramolecular oxidoreductases transposing C=C bonds. The systematic name of this enzyme class is isopentenyl-diphosphate Delta3-Delta2-isomerase. Other names in common use include isopentenylpyrophosphate Delta-isomerase, methylbutenylpyrophosphate isomerase, and isopentenylpyrophosphate isomerase.[2][3][4]

Enzyme mechanism

IPP isomerase catalyzes the isomerization of IPP to DMAPP by an antarafacial transposition of hydrogen.[5][6] The empirical evidence suggests that this reaction proceeds by a protonation/deprotonation mechanism, with the addition of a proton to the re-face of the inactivated C3-C4 double bond resulting in a transient carbocation intermediate.[7][8] The removal of the pro-R proton from C2 forms the C2-C3 double bond of DMAPP.

IPP isomerase mechanism
The mechanism for the isomerization between IPP and DMAPP. Generic proton donors and acceptors are shown because the identities of the amino acids that carry out these functions have not conclusively been established.

Enzyme structure

A cartoon diagram of human IPP isomerase with the catalytic cysteine residue (Cys87) in red and the catalytic glutamic acid residue (Glu149) in blue (RCSB Protein Data Bank accession number 2ICJ).

substrate, consistent with the antarafacial stereochemistry of isomerization.[9][11] The origin of the initial protonation step has not been conclusively established. Recent evidence suggests that the glutamic acid residue is involved in the protonating step despite the observation that its carboxylic acid side-chain is stabilized in its carboxylate form.[12] This discrepancy has been addressed by the discovery of a water molecule in the active site of human IPP isomerase, suggesting a mechanism where the glutamine residue polarizes the double bond of IPP and makes it more susceptible to protonation by water.[13]

IPP isomerase also requires a

coordinating with Mg2+ or Mn2+.[9][14]
The coordination of the metal cation to the glutamate residue stabilizes the carbiocation intermediate after protonation.

Structural studies

As of late 2007, 25

structures have been solved for this class of enzymes, with PDB accession codes 1HX3, 1HZT, 1I9A, 1NFS, 1NFZ, 1OW2, 1P0K, 1P0N, 1PPV, 1PPW, 1PVF, 1Q54, 1R67, 1VCF, 1VCG, 1X83, 1X84, 2B2K, 2DHO, 2G73, 2G74, 2I6K, 2ICJ, 2ICK, and 2PNY
.

Biological function

The protonation of an inactivated double bond is rarely seen in nature, highlighting the unique catalytic mechanism of IPP isomerase. The isomerization of IPP to DMAPP is a crucial step in the synthesis of isoprenoids and isoprenoid-derivatives, compounds that play vital roles in the biosynthetic pathways of all living organisms.

mitochondria.[16]

Mevalonate pathway

Disease relevance

amyotrophic lateral sclerosis, suggesting that the isomerase may play a role in this disease.[20]

References

  1. ^ "IDI1 - Isopentenyl-diphosphate Delta-isomerase - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) - IDI1 gene & protein". UniProt. Retrieved 6 June 2016.
  2. PMID 11158573
    .
  3. PMID 6351725
    .
  4. PMID 13792054
    .
  5. PMID 4288360
    .
  6. ^ Cornforth RH, Popják G (1969). "Chemical syntheses of substrates of sterol biosynthesis". In Raymond BC (ed.). Methods in Enzymology. Vol. 15. Academic Press. pp. 359–390.
  7. PMID 3022798
    .
  8. doi:10.1021/ja00179a049
    .
  9. ^
    PMID 1285217
    .
  10. PMID 17250851
    .
  11. PMID 7908830
    .
  12. PMID 12540835
    .
  13. PMID 17137593
    .
  14. PMID 11698677
    .
  15. S2CID 3999323
    .
  16. PMID 9418296
    .
  17. S2CID 19430360
    .
  18. S2CID 1637634
    .
  19. PMID 18303110
    .
  20. PMID 20955688
    .

External links
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