Language:

Feedback Inhibition of Deoxy-d-xylulose-5-phosphate Synthase Regulates the Methylerythritol 4-Phosphate Pathway

The Journal of biological chemistry, 2013-06, Vol.288 (23), p.16926-16936 [Peer Reviewed Journal]

2013 © 2013 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. ;2013 by The American Society for Biochemistry and Molecular Biology, Inc. 2013 ;ISSN: 0021-9258 ;EISSN: 1083-351X ;DOI: 10.1074/jbc.M113.464636 ;PMID: 23612965

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Feedback Inhibition of Deoxy-d-xylulose-5-phosphate Synthase Regulates the Methylerythritol 4-Phosphate Pathway
Author: Banerjee, Aparajita ; Wu, Yan ; Banerjee, Rahul ; Li, Yue ; Yan, Honggao ; Sharkey, Thomas D.
Subjects: Deoxyxylulose-5-phosphate Synthase ; Enzyme Inhibitors ; Enzyme Structure ; Erythritol - analogs & derivatives ; Erythritol - chemistry ; Erythritol - genetics ; Erythritol - metabolism ; Escherichia coli ; Hemiterpenes - chemistry ; Hemiterpenes - genetics ; Hemiterpenes - metabolism ; Isoprene ; Isoprenoid ; Kinetics ; Methylerythritol Pathway ; Models, Molecular ; Organophosphorus Compounds - chemistry ; Organophosphorus Compounds - metabolism ; Plant Biochemistry ; Plant Biology ; Plant Proteins - chemistry ; Plant Proteins - genetics ; Plant Proteins - metabolism ; Populus - enzymology ; Populus - genetics ; Protein Binding ; Recombinant Proteins - chemistry ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Sugar Phosphates - chemistry ; Sugar Phosphates - genetics ; Sugar Phosphates - metabolism ; Thiamine ; Thiamine Diphosphate ; Thiamine Pyrophosphate - chemistry ; Thiamine Pyrophosphate - genetics ; Thiamine Pyrophosphate - metabolism ; Transferases - chemistry ; Transferases - genetics ; Transferases - metabolism
Is Part Of: The Journal of biological chemistry, 2013-06, Vol.288 (23), p.16926-16936
Description: The 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway leads to the biosynthesis of isopentenyl diphosphate (IDP) and dimethylallyl diphosphate (DMADP), the precursors for isoprene and higher isoprenoids. Isoprene has significant effects on atmospheric chemistry, whereas other isoprenoids have diverse roles ranging from various biological processes to applications in commercial uses. Understanding the metabolic regulation of the MEP pathway is important considering the numerous applications of this pathway. The 1-deoxy-d-xylulose-5-phosphate synthase (DXS) enzyme was cloned from Populus trichocarpa, and the recombinant protein (PtDXS) was purified from Escherichia coli. The steady-state kinetic parameters were measured by a coupled enzyme assay. An LC-MS/MS-based assay involving the direct quantification of the end product of the enzymatic reaction, 1-deoxy-d-xylulose 5-phosphate (DXP), was developed. The effect of different metabolites of the MEP pathway on PtDXS activity was tested. PtDXS was inhibited by IDP and DMADP. Both of these metabolites compete with thiamine pyrophosphate for binding with the enzyme. An atomic structural model of PtDXS in complex with thiamine pyrophosphate and Mg2+ was built by homology modeling and refined by molecular dynamics simulations. The refined structure was used to model the binding of IDP and DMADP and indicated that IDP and DMADP might bind with the enzyme in a manner very similar to the binding of thiamine pyrophosphate. The feedback inhibition of PtDXS by IDP and DMADP constitutes an important mechanism of metabolic regulation of the MEP pathway and indicates that thiamine pyrophosphate-dependent enzymes may often be affected by IDP and DMADP. Background: The methylerythritol phosphate (MEP) pathway is required for the biosynthesis of plastid-derived isoprenoids from plants. Results: Deoxyxylulose-5-phosphate synthase (DXS) was cloned from Populus trichocarpa, and metabolic regulation was tested. Conclusion: Both isopentenyl diphosphate and dimethylallyl diphosphate inhibit DXS by competing with thiamine pyrophosphate. Significance: Prediction of isoprene emission from trees and bioengineering of MEP pathway will be aided by these results.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 0021-9258
EISSN: 1083-351X
DOI: 10.1074/jbc.M113.464636
PMID: 23612965
Source: MEDLINE
PubMed Central
Alma/SFX Local Collection

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Feedback Inhibition of Deoxy-d-xylulose-5-phosphate Synthase Regulates the Methylerythritol 4-Phosphate Pathway

2013 © 2013 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. ;2013 by The American Society for Biochemistry and Molecular Biology, Inc. 2013 ;ISSN: 0021-9258 ;EISSN: 1083-351X ;DOI: 10.1074/jbc.M113.464636 ;PMID: 23612965

Searching Remote Databases, Please Wait