Evidence map›Paper›PMID 27498591›Full record

ArticleJournal of inorganic biochemistry2016

Use of ferrous iron by metallo-β-lactamases.

Samuel T Cahill, Hanna Tarhonskaya, Anna M Rydzik, Emily Flashman, Michael A McDonough, Christopher J Schofield, Jürgen Brem

Open access · hybridAbstract read
In one paragraph

Article in Journal of inorganic biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

15 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. The Fe and Zn cofactor dilemma.Biochimica et biophysica acta. Proteins and proteomics · 2023
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Monitoring protein-metal binding byRSC medicinal chemistry · 2020
    Article
  12. Emergence of metal selectivity and promiscuity in metalloenzymes.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2019
    Review
  13. Article
  14. Article
  15. 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

7 authors at 2 institutions in 1 country.

Samuel T CahillChemistry Research Laboratory, Oxford, United Kingdom.
Hanna TarhonskayaChemistry Research Laboratory, Oxford, United Kingdom.
Anna M RydzikChemistry Research Laboratory, Oxford, United Kingdom.
Emily FlashmanChemistry Research Laboratory, Oxford, United Kingdom.
Michael A McDonoughChemistry Research Laboratory, Oxford, United Kingdom.
Christopher J SchofieldChemistry Research Laboratory, Oxford, United Kingdom. Electronic address: christopher.schofield@chem.ox.ac.uk.
Jürgen BremChemistry Research Laboratory, Oxford, United Kingdom. Electronic address: jurgen.brem@chem.ox.ac.uk.
St Christopher's Hospice · GBUniversity of Oxford · GB

Funding

Biotechnology and Biological Sciences Research Council BB/J014427/1Cancer Research UK 16466Medical Research Council G1100135Medical Research Council MR/L007665/1
6 · The paper itself

Abstract

Metallo-β-lactamases (MBLs) catalyse the hydrolysis of almost all β-lactam antibacterials including the latest generation carbapenems and are a growing worldwide clinical problem. It is proposed that MBLs employ one or two zinc ion cofactors in vivo. Isolated MBLs are reported to use transition metal ions other than zinc, including copper, cadmium and manganese, with iron ions being a notable exception. We report kinetic and biophysical studies with the di-iron(II)-substituted metallo-β-lactamase II from Bacillus cereus (di-Fe(II) BcII) and the clinically relevant B1 subclass Verona integron-encoded metallo-β-lactamase 2 (di-Fe(II) VIM-2). The results reveal that MBLs can employ ferrous iron in catalysis, but with altered kinetic and inhibition profiles compared to the zinc enzymes. A crystal structure of di-Fe(II) BcII reveals only small overall changes in the active site compared to the di-Zn(II) enzyme including retention of the di-metal bridging water; however, the positions of the metal ions are altered in the di-Fe(II) compared to the di-Zn(II) structure. Stopped-flow analyses reveal that the mechanism of nitrocefin hydrolysis by both di-Fe(II) BcII and di-Fe(II) VIM-2 is altered compared to the di-Zn(II) enzymes. Notably, given that the MBLs are the subject of current medicinal chemistry efforts, the results raise the possibility the Fe(II)-substituted MBLs may be of clinical relevance under conditions of low zinc availability, and reveal potential variation in inhibitor activity against the differently metallated MBLs.

Indexed as

Bacillus cereusBacterial Proteinsbeta-LactamasesIronMetalloproteinsBacterial Proteinsbeta-LactamasesIronMetalloproteinsAntibiotic resistanceCarbapenemMetalloenzymeMetallo-β-lactamaseZinc hydrolaseβ-Lactam antibiotics

Identifiers

PMID27498591
PMCPMC5108564
OpenAlexW2496104120

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.