Document Detail


Isopentenyl diphosphate isomerase catalyzed reactions in D2O: product release limits the rate of this sluggish enzyme-catalyzed reaction.
MedLine Citation:
PMID:  22471428     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The E. coli isopentenyl diphosphate isomerase (IDI) catalyzed reaction of isopentenyl diphosphate (IPP) in D(2)O gives a 66% yield of dimethylallyl diphosphate labeled with deuterium at the (E)-methyl group (d-DMAPP) and a 34% yield of IPP labeled with 1 mol of deuterium at C-2 (d-IPP). This shows that the release to D(2)O of the initial product of the IDI-catalyzed reaction (d-DMAPP) is slower than its conversion to d-IPP. Product dissociation is therefore rate determining for isomerization of IPP with a rate constant k(dis) ≈ k(cat) = 0.08 s(-1). The data provide an estimated rate constant of k(as) = 6 × 10(3) M(-1) s(-1) for binding of DMAPP to E. coli IDI that is similar to rate constants determined for the binding of N-protonated 2-amino ethyl diphosphate intermediate analogs to IDI from yeast [Reardon, J. E.; Abeles, R. H. Biochemistry1986, 25, 5609-5616]. We propose that ligand binding to IDI is relatively slow because there is a significant kinetic barrier to reorganization of the initial encounter complex between enzyme, substrate, and an essential Mg(2+) to form the Michaelis complex where the metal cation bridges the protein and the substrate diphosphate group.
Authors:
Venkatadurga Jonnalagadda; Krisztina Toth; John P Richard
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-05
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  134     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-18     Completed Date:  2012-09-26     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6568-70     Citation Subset:  IM    
Copyright Information:
© 2012 American Chemical Society
Affiliation:
Department of Chemistry, University at Buffalo, Buffalo, New York 14260, USA.
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MeSH Terms
Descriptor/Qualifier:
Carbon-Carbon Double Bond Isomerases / metabolism*
Catalysis
Deuterium Oxide*
Escherichia coli / enzymology
Hemiterpenes / metabolism
Kinetics
Organophosphorus Compounds / metabolism
Grant Support
ID/Acronym/Agency:
GM39754/GM/NIGMS NIH HHS; R01 GM039754-23/GM/NIGMS NIH HHS; R01 GM039754-24/GM/NIGMS NIH HHS; R01 GM039754-25/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Hemiterpenes; 0/Organophosphorus Compounds; 358-71-4/isopentenyl pyrophosphate; 7789-20-0/Deuterium Oxide; EC 5.3.3.-/Carbon-Carbon Double Bond Isomerases; EC 5.3.3.2/isopentenyldiphosphate delta-isomerase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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