Evidence map›Paper›PMID 25210044›Full record

ArticleThe Journal of biological chemistry2014

Cholesterol ester oxidation by mycobacterial cytochrome P450.

Daniel J Frank, Yarrow Madrona, Paul R Ortiz de Montellano

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

16 citing papers in PubMed, 35 citations in OpenAlex.

  1. Clonal spread of Mycobacterium monacense strains among patients with extrapulmonary mycobacteriosis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Cytochrome P450 research andThe Journal of biological chemistry · 2019
    Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Recent Structural Insights into Cytochrome P450 Function.Trends in pharmacological sciences · 2016
    Review
  13. Article
  14. Article
  15. Article
  16. 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

3 authors at 1 institution in 1 country.

Daniel J FrankDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158-2517.
Yarrow MadronaDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158-2517.
Paul R Ortiz de MontellanoDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158-2517. Electronic address: Ortiz@cgl.ucsf.edu.
University of California, San Francisco · US

Funding

SELECTIVE DESTRUCTION OF CYTOCHROME P450 BY DRUGSR01GM025515 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ORTIZ DE MONTELLANO, PAUL R · 1985 to 2014
$5.6M
Oxygen Sensors and P450 Monooxygenases in Mycobacertium tuberculosisR01AI074824 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ORTIZ DE MONTELLANO, PAUL R · 2007 to 2016
$4.3M
SELECTIVE DESTRUCTION OF CYTOCHROME P450 BY DRUGSR37GM025515 · NIGMS · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI ORTIZ DE MONTELLANO, PAUL R · 1989 to 1998
–
NIAID NIH HHS AI074824NIAID NIH HHS R01 AI074824NIGMS NIH HHS GM25515NIGMS NIH HHS R01 GM025515NIGMS NIH HHS R37 GM025515
6 · The paper itself

Abstract

Mycobacteria share a common cholesterol degradation pathway initiated by oxidation of the alkyl side chain by enzymes of cytochrome P450 (CYP) families 125 and 142. Structural and sequence comparisons of the two enzyme families revealed two insertions into the N-terminal region of the CYP125 family (residues 58-67 and 100-109 in the CYP125A1 sequence) that could potentially sterically block the oxidation of the longer cholesterol ester molecules. Catalytic assays revealed that only CYP142 enzymes are able to oxidize cholesteryl propionate, and although CYP125 enzymes could oxidize cholesteryl sulfate, they were much less efficient at doing so than the CYP142 enzymes. The crystal structure of CYP142A2 in complex with cholesteryl sulfate revealed a substrate tightly fit into a smaller active site than was previously observed for the complex of CYP125A1 with 4-cholesten-3-one. We propose that the larger CYP125 active site allows for multiple binding modes of cholesteryl sulfate, the majority of which trigger the P450 catalytic cycle, but in an uncoupled mode rather than one that oxidizes the sterol. In contrast, the more unhindered and compact CYP142 structure enables enzymes of this family to readily oxidize cholesteryl esters, thus providing an additional source of carbon for mycobacterial growth.

Indexed as

Catalytic DomainCholesterol EstersCrystallography, X-RayCytochrome P-450 Enzyme SystemKineticsModels, MolecularMycobacterium smegmatisMycobacterium tuberculosisNADPOxidation-ReductionProtein BindingProtein Structure, SecondaryCholesterol Esterscholesteryl sulfateCytochrome P-450 Enzyme SystemNADPCholesterolCholesterol MetabolismCytochrome P450Mycobacterium smegmatisMycobacterium tuberculosis

Identifiers

PMID25210044
PMCPMC4215225
OpenAlexW2043664213

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.