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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Carbon-Carbon Double Bond Isomerases / antagonists & inhibitors
-
Carbon-Carbon Double Bond Isomerases / chemistry*
-
Carbon-Carbon Double Bond Isomerases / metabolism*
-
Catalytic Domain
-
Crystallography
-
Cysteine / chemistry
-
Epoxy Compounds / pharmacology
-
Escherichia coli / enzymology*
-
Glutamic Acid / chemistry
-
Hemiterpenes
-
Kinetics
-
Organophosphorus Compounds / pharmacology
-
Protein Structure, Secondary
-
Tyrosine / chemistry
Substances
-
Epoxy Compounds
-
Hemiterpenes
-
Organophosphorus Compounds
-
3-methyl-3,4-epoxybutyl diphosphate
-
Glutamic Acid
-
Tyrosine
-
Carbon-Carbon Double Bond Isomerases
-
isopentenyldiphosphate delta-isomerase
-
Cysteine