Evidence map›Paper›PMID 24576089›Full record

ArticleBiochemistry2014

Strength of axial water ligation in substrate-free cytochrome P450s is isoform dependent.

Kip P Conner, Alina M Schimpf, Alex A Cruce, Kirsty J McLean, Andrew W Munro, Daniel J Frank, Matthew D Krzyaniak, Paul Ortiz de Montellano, Michael K Bowman, William M Atkins

Open access · bronzeAbstract read
In one paragraph

Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

14 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Catalysis and Electron Transfer inChemical reviews · 2022
    Review
  4. Article
  5. Characterization of CYP125A13, the First Steroid C-27 Monooxygenase fromJournal of microbiology and biotechnology · 2020
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
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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

10 authors at 3 institutions in 1 country.

Kip P ConnerDepartments of Medicinal Chemistry Box 357610 and ‡Chemistry Box 351700, University of Washington Seattle , Washington 98195 United States.
Alina M Schimpf
Alex A Cruce
Kirsty J McLean
Andrew W Munro
Daniel J Frank
Matthew D Krzyaniak
Paul Ortiz de Montellano
Michael K Bowman
William M Atkins
University of Alabama · USUniversity of Washington · USUniversity of California, San Francisco · US

Funding

Pharmacological Sciences SupplementT32GM007750 · NIGMS · UNIVERSITY OF WASHINGTON · PI ATKINS, WILLIAM M · 1985 to 2023
$12.6M
SELECTIVE DESTRUCTION OF CYTOCHROME P450 BY DRUGSR01GM025515 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ORTIZ DE MONTELLANO, PAUL R · 1985 to 2014
$5.6M
Structural Basis of Cytochrome P450 ActivityR01GM076343 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI SCOTT, EMILY E · 2006 to 2014
$2.9M
P450-Base Drug Interactions with Low Spin DrugsR01GM110790 · NIGMS · UNIVERSITY OF WASHINGTON · PI ATKINS, WILLIAM M · 2013 to 2016
$1.7M
NIGMS NIH HHS 1R01 GM110790NIGMS NIH HHS R01 GM025515NIGMS NIH HHS R01 GM076343NIGMS NIH HHS R01 GM110790NIGMS NIH HHS R01GM25515NIGMS NIH HHS T32 GM007750
6 · The paper itself

Abstract

The heme-containing cytochrome P450s exhibit isoform-dependent ferric spin equilibria in the resting state and differential substrate-dependent spin equilibria. The basis for these differences is not well understood. Here, magnetic circular dichroism (MCD) reveals significant differences in the resting low spin ligand field of CYPs 3A4, 2E1, 2C9, 125A1, and 51B1, which indicates differences in the strength of axial water ligation to the heme. The near-infrared bands that specifically correspond to charge-transfer porphyrin-to-metal transitions span a range of energies of nearly 2 kcal/mol. In addition, the experimentally determined MCD bands are not entirely in agreement with the expected MCD energies calculated from electron paramagnetic resonance parameters, thus emphasizing the need for the experimental data. MCD marker bands of the high spin heme between 500 and 680 nm were also measured and suggest only a narrow range of energies for this ensemble of high spin Cys(S(-)) → Fe(3+) transitions among these isoforms. The differences in axial ligand energies between CYP isoforms of the low spin states likely contribute to the energetics of substrate-dependent spin state perturbation. However, these ligand field energies do not correlate with the fraction of high spin vs low spin in the resting state enzyme, suggestive of differences in water access to the heme or isoform-dependent differences in the substrate-free high spin states as well.

Indexed as

Circular DichroismCytochrome P-450 Enzyme SystemElectron Spin Resonance SpectroscopyLigationProtein IsoformsWaterCytochrome P-450 Enzyme SystemProtein IsoformsWater

Identifiers

PMID24576089
PMCPMC3985942
OpenAlexW2081789651

What OpenQuestion holds

Textmetadata
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.