Evidence map›Paper›PMID 24361620›Full record

ArticleBiochimica et biophysica acta2014

Identification, modeling and ligand affinity of early deuterostome CYP51s, and functional characterization of recombinant zebrafish sterol 14α-demethylase.

Ann Michelle Stanley Morrison, Jared V Goldstone, David C Lamb, Akira Kubota, Benjamin Lemaire, John J Stegeman

Open access · greenAbstract read
In one paragraph

Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.5field-weighted citation impact, top 9% 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

13 citing papers in PubMed, 32 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

6 authors at 2 institutions in 2 countries.

Ann Michelle Stanley MorrisonBiology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA; School of Public Health, Harvard University, Boston, MA 02115, USA.
Jared V GoldstoneBiology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
David C LambBiology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA; Institute of Life Science, College of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK.
Akira KubotaBiology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
Benjamin LemaireBiology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
John J StegemanBiology Department, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA. Electronic address: jstegeman@whoi.edu.
Woods Hole Oceanographic Institution · USHarvard University · US

Funding

Training CoreP42ES007381 · NIEHS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI SHERR, DAVID H · 1995 to 2019
$46.1M
Nomenclature of Human and Vertebrate GenesU41HG003345 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI BIRNEY, EWAN, BRUFORD, ELSPETH · 2013 to 2017
$2.4M
NHGRI NIH HHS U41 HG003345NIEHS NIH HHS P42 ES007381NIEHS NIH HHS P42ES007381NIEHS NIH HHS P42ES059471Wellcome Trust
6 · The paper itself

Abstract

backgroundSterol 14α-demethylase (cytochrome P450 51, CYP51, P45014DM) is a microsomal enzyme that in eukaryotes catalyzes formation of sterols essential for cell membrane function and as precursors in biosynthesis of steroid hormones. Functional properties of CYP51s are unknown in non-mammalian deuterostomes.

methodsPCR-cloning and sequencing and computational analyses (homology modeling and docking) addressed CYP51 in zebrafish Danio rerio, the reef fish sergeant major Abudefduf saxatilis, and the sea urchin Strongylocentrotus purpuratus. Following N-terminal amino acid modification, zebrafish CYP51 was expressed in Escherichia coli, and lanosterol 14α-demethylase activity and azole inhibition of CYP51 activity were characterized using GC-MS.

resultsMolecular phylogeny positioned S. purpuratus CYP51 at the base of the deuterostome clade. In zebrafish, CYP51 is expressed in all organs examined, most strongly in intestine. The recombinant protein bound lanosterol and catalyzed 14α-demethylase activity, at 3.2nmol/min/nmol CYP51. The binding of azoles to zebrafish CYP51 gave KS (dissociation constant) values of 0.26μM for ketoconazole and 0.64μM for propiconazole. Displacement of carbon monoxide also indicated zebrafish CYP51 has greater affinity for ketoconazole. Docking to homology models showed that lanosterol docks in fish and sea urchin CYP51s with an orientation essentially the same as in mammalian CYP51s. Docking of ketoconazole indicates it would inhibit fish and sea urchin CYP51s.

conclusionsBiochemical and computational analyses are consistent with lanosterol being a substrate for early deuterostome CYP51s. GENERAL SIGNIFICANCE: The results expand the phylogenetic view of animal CYP51, with evolutionary, environmental and therapeutic implications.

Indexed as

AnimalsFemaleHumansLigandsMaleModels, MolecularMolecular Docking SimulationRecombinant ProteinsSterol 14-DemethylaseSterolsZebrafishLigandsRecombinant ProteinsSterol 14-DemethylaseSterolsAzole inhibitionCYP51DeuterostomeSterol 14α-demethylaseSterol biosynthesisZebrafish

Identifiers

PMID24361620
PMCPMC4118742
OpenAlexW2025695540

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.