Isopentenyl-diphosphate delta-isomerase (type 1)

 

This entry represents type 1 of two non-homologous families of the enzyme isopentenyl-diphosphate delta-isomerase (IPP isomerase; EC:5.3.3.2). IPP isomerase is a member of the Nudix hydrolase superfamily, and is a key enzyme in the isoprenoid biosynthetic pathway. It catalyses the interconversion of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate. Dimethylallyl phosphate is the initial substrate for the biosynthesis of carotenoids and other long chain isoprenoids.

 

Reference Protein and Structure

Sequence
Q46822 UniProt (5.3.3.2) IPR011876 (Sequence Homologues) (PDB Homologues)
Biological species
Escherichia coli K-12 (Bacteria) Uniprot
PDB
1nfs - STRUCTURE AND MECHANISM OF ACTION OF ISOPENTENYLPYROPHOSPHATE-DIMETHYLALLYLPYROPHOSPHATE ISOMERASE: COMPLEX WITH NIPP (1.96 Å) PDBe PDBsum 1nfs
Catalytic CATH Domains
3.90.79.10 CATHdb (see all for 1nfs)
Cofactors
Manganese(2+) (1), Magnesium(2+) (1) Metal MACiE
Click To Show Structure

Enzyme Reaction (EC:5.3.3.2)

isopentenyl diphosphate(3-)
CHEBI:128769ChEBI
→
prenyl diphosphate(3-)
CHEBI:57623ChEBI
Alternative enzyme names: Isopentenylpyrophosphate Delta-isomerase, Isopentenylpyrophosphate isomerase, Methylbutenylpyrophosphate isomerase, IPP isomerase,

Enzyme Mechanism

Introduction

The double bond of the isopentenyl diphosphate substrate deprotonates Tyr104. The double bond of the isopentenyl diphosphate substrate deprotonates Tyr104. Tyr104 deprotonates water, which in turn deprotonates Cys67 in an inferred return step.

The residues that donate and abstract protons in this reaction are likely to exist as an equilibrium mixture of protonated and deprotonated forms thus they would be capable of reversing roles for isomerisation of the product of this reaction.

Catalytic Residues Roles

UniProt PDB* (1nfs)
Trp161 Trp161A Trp161 may stabilise the highly reactive carbocation through quadrupole-charge interaction [PMID:11285217]. electrostatic stabiliser, polar/non-polar interaction
Cys67, Tyr104 Cys67A, Tyr104A Act as a general acid/base. hydrogen bond acceptor, hydrogen bond donor, proton acceptor, proton donor
Glu116 Glu116A Forms part of the Mn binding site. It is probably un-protonated given its location in the inner coordination sphere of the metal, and acts as a proton relay between the substrate and Tyr104. hydrogen bond acceptor, metal ligand, proton acceptor, proton donor, electrostatic stabiliser
His32, His25, His69, Glu114 His32A, His25A, His69A, Glu114A Forms part of the manganese binding site. metal ligand
Glu87 Glu87A Forms part of the magnesium binding site. metal ligand
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

proton transfer, overall reactant used, intermediate formation, proton relay, intermediate terminated, overall product formed, native state of enzyme regenerated, inferred reaction step

References

  1. Wouters J et al. (2003), J Biol Chem, 278, 11903-11908. 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. DOI:10.1074/jbc.m212823200. PMID:12540835.
  2. Berthelot K et al. (2012), Biochimie, 94, 1621-1634. Isopentenyl diphosphate isomerase: A checkpoint to isoprenoid biosynthesis. DOI:10.1016/j.biochi.2012.03.021. PMID:22503704.
  3. Wouters J et al. (2003), J Am Chem Soc, 125, 3198-3199. Structure and Mechanism of Action of Isopentenylpyrophosphate-Dimethylallylpyrophosphate Isomerase. DOI:10.1021/ja029171p. PMID:12630859.
  4. Durbecq V et al. (2001), EMBO J, 20, 1530-1537. Crystal structure of isopentenyl diphosphate:dimethylallyl diphosphate isomerase. DOI:10.1093/emboj/20.7.1530. PMID:11285217.

Contributors

Gemma L. Holliday, Daniel E. Almonacid, Anna Waters, Craig Porter, James Willey