J Am Chem Soc. 2009 Dec 16;131(49):17734-5. doi: 10.1021/ja907470n.

IspG converts an epoxide substrate analogue to (E)-4-hydroxy-3-methylbut-2-enyl diphosphate: implications for IspG catalysis in isoprenoid biosynthesis.

Nyland RL 2nd, Xiao Y, Liu P, Freel Meyers CL.

Source

Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

Abstract

IspG is an intriguing enzyme in bacteria, parasite, and plant isoprenoid biosynthesis, and its catalytic mechanism remains elusive. We report here the synthesis of (2R,3R)-4-hydroxy-3-methyl-2,3-epoxybutanyl diphosphate (Epoxy-HMBPP), a proposed intermediate in one of the frequently cited mechanistic models. We have also demonstrated that this epoxide analogue is a catalytically competent IspG substrate. This study represents the first mechanistic study of this important enzyme.

PMID:: 19919056; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances

Publication Types

MeSH Terms

Substances

LinkOut - more resources

Full Text Sources

Supplemental Content

Save items

Related citations in PubMed

Methylerythritol cyclodiphosphate (MEcPP) in deoxyxylulose phosphate pathway: synthesis from an epoxide and mechanisms. [Chem Commun (Camb). 2010]
Methylerythritol cyclodiphosphate (MEcPP) in deoxyxylulose phosphate pathway: synthesis from an epoxide and mechanisms.
Xiao Y, Nyland RL 2nd, Meyers CL, Liu P. Chem Commun (Camb). 2010 Oct 14; 46(38):7220-2. Epub 2010 Sep 1.
Isoprenoid biosynthesis in plant chloroplasts via the MEP pathway: direct thylakoid/ferredoxin-dependent photoreduction of GcpE/IspG. [FEBS Lett. 2006]
Isoprenoid biosynthesis in plant chloroplasts via the MEP pathway: direct thylakoid/ferredoxin-dependent photoreduction of GcpE/IspG.
Seemann M, Tse Sum Bui B, Wolff M, Miginiac-Maslow M, Rohmer M. FEBS Lett. 2006 Mar 6; 580(6):1547-52. Epub 2006 Feb 2.
Paramagnetic intermediates of (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (GcpE/IspG) under steady-state and pre-steady-state conditions. [J Am Chem Soc. 2010]
Paramagnetic intermediates of (E)-4-hydroxy-3-methylbut-2-enyl diphosphate synthase (GcpE/IspG) under steady-state and pre-steady-state conditions.
Xu W, Lees NS, Adedeji D, Wiesner J, Jomaa H, Hoffman BM, Duin EC. J Am Chem Soc. 2010 Oct 20; 132(41):14509-20.
Review Perspectives in anti-infective drug design. The late steps in the biosynthesis of the universal terpenoid precursors, isopentenyl diphosphate and dimethylallyl diphosphate. [Bioorg Chem. 2004]
Review Perspectives in anti-infective drug design. The late steps in the biosynthesis of the universal terpenoid precursors, isopentenyl diphosphate and dimethylallyl diphosphate.
Rohdich F, Bacher A, Eisenreich W. Bioorg Chem. 2004 Oct; 32(5):292-308.
Review Diversity of the biosynthesis of the isoprene units. [Nat Prod Rep. 2003]
Review Diversity of the biosynthesis of the isoprene units.
Kuzuyama T, Seto H. Nat Prod Rep. 2003 Apr; 20(2):171-83.

See reviews... See all...

Cited by 4 PubMed Central articles

IspG-catalyzed positional isotopic exchange in methylerythritol cyclodiphosphate of the deoxyxylulose phosphate pathway: mechanistic implications. [Chembiochem. 2011]
IspG-catalyzed positional isotopic exchange in methylerythritol cyclodiphosphate of the deoxyxylulose phosphate pathway: mechanistic implications.
Xiao Y, Rooker D, You Q, Meyers CL, Liu P. Chembiochem. 2011 Mar 7; 12(4):527-30. Epub 2011 Jan 26.
An ENDOR and HYSCORE investigation of a reaction intermediate in IspG (GcpE) catalysis. [J Am Chem Soc. 2011]
An ENDOR and HYSCORE investigation of a reaction intermediate in IspG (GcpE) catalysis.
Wang W, Wang K, Li J, Nellutla S, Smirnova TI, Oldfield E. J Am Chem Soc. 2011 Jun 8; 133(22):8400-3. Epub 2011 May 16.
Methylerythritol cyclodiphosphate (MEcPP) in deoxyxylulose phosphate pathway: synthesis from an epoxide and mechanisms. [Chem Commun (Camb). 2010]
Methylerythritol cyclodiphosphate (MEcPP) in deoxyxylulose phosphate pathway: synthesis from an epoxide and mechanisms.
Xiao Y, Nyland RL 2nd, Meyers CL, Liu P. Chem Commun (Camb). 2010 Oct 14; 46(38):7220-2. Epub 2010 Sep 1.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Gene
Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
Protein (RefSeq)
NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Taxonomy via GenBank
Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
GEO Profiles
Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.

Recent activity

Clear Turn Off Turn On

IspG converts an epoxide substrate analogue to (E)-4-hydroxy-3-methylbut-2-enyl ...
IspG converts an epoxide substrate analogue to (E)-4-hydroxy-3-methylbut-2-enyl diphosphate: implications for IspG catalysis in isoprenoid biosynthesis.
J Am Chem Soc. 2009 Dec 16 ;131(49):17734-5. doi: 10.1021/ja907470n.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Result Filters

Display Settings:

Send to: