Evidence map›Paper›PMID 25868383›Full record

ArticleJournal of molecular biology2015

Atomic-Resolution Structures of Discrete Stages on the Reaction Coordinate of the [Fe4S4] Enzyme IspG (GcpE).

Felix Quitterer, Annika Frank, Ke Wang, Guodong Rao, Bing O'Dowd, Jikun Li, Francisco Guerra, Safwat Abdel-Azeim, Adelbert Bacher, Jörg Eppinger and 2 more

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Substitution of CHChemistry (Weinheim an der Bergstrasse, Germany) · 2025
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  9. Uncovering the functional residues ofProceedings of the National Academy of Sciences of the United States of America · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Felix QuittererCenter for Integrated Protein Science, Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Garching D-85747, Germany.
Annika FrankCenter for Integrated Protein Science, Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Garching D-85747, Germany.
Ke WangDepartment of Chemistry, University of Illinois, Urbana, IL 61801, USA.
Guodong RaoDepartment of Chemistry, University of Illinois, Urbana, IL 61801, USA.
Bing O'DowdDepartment of Chemistry, University of Illinois, Urbana, IL 61801, USA.
Jikun LiDepartment of Chemistry, University of Illinois, Urbana, IL 61801, USA.
Francisco GuerraDepartment of Chemistry, University of Illinois, Urbana, IL 61801, USA.
Safwat Abdel-AzeimDivision of Physical Sciences and Engineering, KAUST Catalysis Center, King Abdullah University of Science and Technology, Thuwal 23955, Kingdom of Saudi Arabia.
Adelbert BacherCenter for Integrated Protein Science, Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Garching D-85747, Germany.
Jörg EppingerDivision of Physical Sciences and Engineering, KAUST Catalysis Center, King Abdullah University of Science and Technology, Thuwal 23955, Kingdom of Saudi Arabia.
Eric OldfieldDepartment of Chemistry, University of Illinois, Urbana, IL 61801, USA.
Michael GrollCenter for Integrated Protein Science, Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Garching D-85747, Germany.
University of Illinois Urbana-Champaign · USCenter for Integrated Protein Science Munich · DEKing Abdullah University of Science and Technology · SATechnical University of Munich · DE

Funding

Structure, Function and Inhibition of [4Fe-4S] ProteinsR01GM065307 · NIGMS · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI OLDFIELD, ERIC · 2002 to 2017
$5.4M
NIGMS NIH HHS GM065307NIGMS NIH HHS R01 GM065307
6 · The paper itself

Abstract

IspG is the penultimate enzyme in non-mevalonate biosynthesis of the universal terpene building blocks isopentenyl diphosphate and dimethylallyl diphosphate. Its mechanism of action has been the subject of numerous studies but remained unresolved due to difficulties in identifying distinct reaction intermediates. Using a moderate reducing agent and an epoxide substrate analogue, we were now able to trap and crystallographically characterize various stages in the IspG-catalyzed conversion of 2-C-methyl-D-erythritol-2,4-cyclo-diphosphate into (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate. In addition, the enzyme's structure was determined in complex with several inhibitors. These results, combined with recent electron paramagnetic resonance data, allowed us to deduce a detailed and complete IspG catalytic mechanism, which describes all stages from initial ring opening to formation of (E)-1-hydroxy-2-methylbut-2-enyl-4-diphosphate via discrete radical and carbanion intermediates. The data presented in this article provide a guide for the design of selective drugs against many prokaryotic and eukaryotic pathogens to which the non-mevalonate pathway is essential for survival and virulence.

Indexed as

Cloning, MolecularCrystallography, X-RayEnzymesModels, MolecularProtein ConformationRecombinant ProteinsThermus thermophilusEnzymeshydroxymethylbutenyl 4-diphosphate synthaseRecombinant Proteinsiron–sulfur cluster catalysismethylerythritol-phosphate pathwayreaction mechanismsterpene biosynthesis

Identifiers

PMID25868383
PMCPMC4433817
OpenAlexW2134410531

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.