Evidence map›Paper›PMID 23205906›Full record

ArticleBiochemistry2012

Magnesium-induced nucleophile activation in the guanylyltransferase mRNA capping enzyme.

Robert V Swift, Chau D Ong, Rommie E Amaro

Abstract read
In one paragraph

Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

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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

3 authors at 2 institutions in 1 country.

Robert V SwiftDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Chau D Ong
Rommie E Amaro
University of California, San Diego · USLake Erie College of Osteopathic Medicine · US

Funding

A Structural Systems Biology Approach to Drug DiscoveryDP2OD007237 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AMARO, ROMMIE E · 2010 to 2015
$2.9M
NIH HHS DP2 OD007237NIH HHS DP2-OD007237
6 · The paper itself

Abstract

The mRNA guanylyltransferase, or mRNA capping enzyme, cotranscriptionally caps the 5'-end of nascent mRNA with GMP during the second reaction in a set of three enzymatic reactions that result in the formation of an N7-methylguanosine cap during mRNA maturation. The mRNA capping enzyme is characterized, in part, by a conserved lysine nucleophile that attacks the α-phosphorus atom of GTP, forming a lysine-GMP intermediate. Experiments have firmly established that magnesium is required for efficient intermediate formation but have provided little insight into the requirement's molecular origins. Using empirical and thermodynamic integration pK(a) estimates, along with conventional molecular dynamics simulations, we show that magnesium binding likely activates the lysine nucleophile by increasing its acidity and by biasing the deprotonated nucleophile into conformations conducive to intermediate formation. These results provide additional functional understanding of an important enzyme in the mRNA transcript life cycle and allow functional analogies to be drawn that affect our understanding of the metal dependence of related superfamily members.

Indexed as

Catalytic DomainGuanosine MonophosphateKineticsLysineMagnesiumMolecular Dynamics SimulationmRNA GuanylyltransferasesNucleotidyltransferasesRNA CapsThermodynamicsGuanosine MonophosphateLysineMagnesiummRNA GuanylyltransferasesNucleotidyltransferasesRNA Caps

Identifiers

PMID23205906
PMCPMC3549306
OpenAlexW2007150471

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.