PDBsum entry: 1nfz

Isomerase

PDB id: 1nfz

Contents

Protein chains

176 a.a. *

Ligands

EIP ×2

Metals

_MN ×2

_MG ×2

Waters ×298

* Residue conservation analysis

PDB id:

1nfz

Name:

Isomerase

Title:

Structure and mechanism of action of isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase: complex with eipp

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)

Resolution:

1.97Å R-factor: 0.180 R-free: 0.237

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

Date:

16-Dec-02 Release date: 24-Jun-03

Protein chains

Q46822  (IDI_ECOLI) -  Isopentenyl-diphosphate Delta-isomerase

Seq: 182 a.a.

Struc: 176 a.a.

Enzyme reactions

• Enzyme class: E.C.5.3.3.2 - Isopentenyl-diphosphate Delta-isomerase.
• Pathway: Terpenoid biosynthesis
• Reaction: Isopentenyl diphosphate = dimethylallyl diphosphate

Isopentenyl diphosphate (Bound ligand (Het Group name = EIP) matches with 93.00% similarity) = dimethylallyl diphosphate

• Cofactor: Calcium or magnesium or manganese; FMN or FAD

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: cytoplasm (1 term)
• Biological process: isoprenoid biosynthetic process (2 terms)
• Biochemical function: hydrolase activity (4 terms)

reference

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.

ABSTRACT

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.