Evidence map›Paper›PMID 25058926›Full record

ArticleAnalytical biochemistry2014

A fluorescent carbapenem for structure function studies of penicillin-binding proteins, β-lactamases, and β-lactam sensors.

Cynthia M June, Robert M Vaughan, Lucas S Ulberg, Robert A Bonomo, Laurie A Witucki, David A Leonard

Abstract read
In one paragraph

Article in Analytical biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

10 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Investigating β-Lactam Drug Targets inACS infectious diseases · 2021
    Article
  6. Effects of crystalline penicillin G sodium on human T-cells differentiation.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2021
    Article
  7. Review
  8. Article
  9. Article
  10. Article
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

6 authors at 2 institutions in 1 country.

Cynthia M JuneDepartment of Chemistry, Grand Valley State University, Allendale, MI 49401, USA.
Robert M VaughanDepartment of Chemistry, Grand Valley State University, Allendale, MI 49401, USA.
Lucas S UlbergDepartment of Chemistry, Grand Valley State University, Allendale, MI 49401, USA.
Robert A BonomoResearch Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and Department of Pharmacology, Molecular Biology, and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Laurie A WituckiDepartment of Chemistry, Grand Valley State University, Allendale, MI 49401, USA.
David A LeonardDepartment of Chemistry, Grand Valley State University, Allendale, MI 49401, USA. Electronic address: leonardd@gvsu.edu.
Grand Valley State University · USCase Western Reserve University · US

Funding

Understanding B-Lactam Resistance in Acinetobacter baumanniiR01AI072219 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI ROBERT A. BONOMO, Philip N. Rather · 2007 to 2026
$6.6M
Understanding ceftazidime resistance in SHV B-LactamasesR01AI063517 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI BONOMO, ROBERT A. · 2005 to 2023
$4.9M
Investigations of the role of key active site residues of two class D lactamasesR15AI082416 · NIAID · GRAND VALLEY STATE UNIVERSITY · PI LEONARD, DAVID A · 2009 to 2015
$991k
NIAID NIH HHS R01 AI063517NIAID NIH HHS R01AI063517NIAID NIH HHS R01 AI072219NIAID NIH HHS R01AI072219NIAID NIH HHS R15 AI082416NIAID NIH HHS R15AI082416
6 · The paper itself

Abstract

By reacting fluorescein isothiocyanate with meropenem, we have prepared a carbapenem-based fluorescent β-lactam. Fluorescein-meropenem binds both penicillin-binding proteins and β-lactam sensors and undergoes a typical acylation reaction in the active site of these proteins. The probe binds the class D carbapenemase OXA-24/40 with close to the same affinity as meropenem and undergoes a complete catalytic hydrolysis reaction. The visible light excitation and strong emission of fluorescein render this molecule a useful structure-function probe through its application in sodium dodecyl sulfate-polyacrylamide gel electrophoresis assays as well as solution-based kinetic anisotropy assays. Its classification as a carbapenem β-lactam and the position of its fluorescent modification render it a useful complement to other fluorescent β-lactams, most notably Bocillin FL. In this study, we show the utility of fluorescein-meropenem by using it to detect mutants of OXA-24/40 that arrest at the acyl-intermediate state with carbapenem substrates but maintain catalytic competency with penicillin substrates.

Indexed as

Electrophoresis, Polyacrylamide GelBacterial Proteinsbeta-LactamasesBiocatalysisBoron CompoundsCarbapenemsFluorescein-5-isothiocyanateHydrolysisKineticsMeropenemPenicillin-Binding ProteinsPenicillinsThienamycinsBacterial Proteinsbeta-LactamasesBOCILLIN FLBoron CompoundscarbapenemaseCarbapenemsFluorescein-5-isothiocyanateMeropenemPenicillin-Binding ProteinsPenicillinsThienamycinsCarbapenemFluorescent modificationPenicillin-binding proteinβ-Lactamase

Identifiers

PMID25058926
PMCPMC4167909
OpenAlexW2047025719

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.