Isopentenyl pyrophosphate isomerase
| Isopentenyl-pyrophosphate delta isomerase 1 | |
|---|---|
| Identifiers | |
| Symbol | IDI1 |
| Entrez | 3422 |
| HUGO | 5387 |
| OMIM | 604055 |
| RefSeq | NM_004508 |
| UniProt | Q13907 |
| Other data | |
| EC number | 5.3.3.2 |
| Locus | Chr. 10 p15.3 |
Isopentenyl pyrophosphate isomerase (IPP isomerase), also known as Isopentenyl-diphosphate delta isomerase, is an isomerase that catalyzes the conversion of the relatively un-reactive isopentenyl pyrophosphate (IPP) to the more-reactive electrophile dimethylallyl pyrophosphate (DMAPP). This isomerization is a key step in the biosynthesis of isoprenoids through the mevalonate pathway.
IPP isomerase catalyzes the isomerization of IPP to DMAPP by an antarafacial transposition of hydrogen. 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-C4double bond resulting in a transient carbocation intermediate. The removal of the pro-R proton from C2 forms the C2-C3 double bond of DMAPP.
Crystallographic studies have observed that the active form of IPP isomerase is a monomer with alternating α-helices and β-sheets. The active site of IPP isomerase is deeply buried within the enzyme and consists of a glutamic acid residue and a cysteine residue that interact with opposite sides of the IPP substrate, consistent with the antarafacial stereochemistry of isomerization. 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. 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.
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