Evidence map›Paper›PMID 31072872›Full record

ArticleThe Journal of biological chemistry2019

Conformational selection dominates binding of steroids to human cytochrome P450 17A1.

F Peter Guengerich, Clayton J Wilkey, Sarah M Glass, Michael J Reddish

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

28 citing papers in PubMed, 45 citations in OpenAlex.

  1. Binding Site Vectors Enable Mapping of Cytochrome P450 Functional Landscapes.Journal of chemical information and modeling · 2026
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  14. CytochromeDrug metabolism and disposition: the biological fate of chemicals · 2021
    Article
  15. Article
  16. Steroidogenic cytochrome P450 17A1 structure and function.Molecular and cellular endocrinology · 2021
    Review
  17. Article
  18. Article
  19. Article
  20. 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

4 authors at 1 institution in 1 country.

F Peter GuengerichFrom the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146 f.guengerich@vanderbilt.edu.ORCID 0000-0002-7458-3048
Clayton J WilkeyFrom the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.ORCID 0000-0001-6062-1093
Sarah M GlassFrom the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.ORCID 0000-0003-1942-7293
Michael J ReddishFrom the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.
Vanderbilt University · US

Funding

TRAINING PROGRAM IN ENVIRONMENTAL TOXICOLOGYT32ES007028 · NIEHS · VANDERBILT UNIVERSITY · PI F PETER Guengerich, Fiona Edith Harrison · 1985 to 2026
$15.7M
Metabolism of Carcinogens and Drugs by Human P450sR01GM118122 · NIGMS · VANDERBILT UNIVERSITY · PI GUENGERICH, F PETER · 2016 to 2023
$3.3M
NIEHS NIH HHS T32 ES007028NIGMS NIH HHS R01 GM118122
6 · The paper itself

Abstract

Cytochrome P450 (P450, CYP) enzymes are the major catalysts involved in the oxidation of steroids as well as many other compounds. Their versatility has been explained in part by flexibility of the proteins and complexity of the binding mechanisms. However, whether these proteins bind their substrates via induced fit or conformational selection is not understood. P450 17A1 has a major role in steroidogenesis, catalyzing the two-step oxidations of progesterone and pregnenolone to androstenedione and dehydroepiandrosterone, respectively, via 17α-hydroxy (OH) intermediates. We examined the interaction of P450 17A1 with its steroid substrates by analyzing progress curves (UV-visible spectroscopy), revealing that the rates of binding of any of these substrates decreased with increasing substrate concentration, a hallmark of conformational selection. Further, when the concentration of 17α-OH pregnenolone was held constant and the P450 concentration increased, the binding rate increased, and such opposite patterns are also diagnostic of conformational selection. Kinetic simulation modeling was also more consistent with conformational selection than with an induced-fit mechanism. Cytochrome

Indexed as

17-alpha-Hydroxypregnenolone17-alpha-HydroxyprogesteroneAndrostenesHumansKineticsProtein ConformationSteroid 17-alpha-HydroxylaseSubstrate Specificity17-alpha-Hydroxypregnenolone17-alpha-HydroxyprogesteroneabirateroneAndrostenesCYP17A1 protein, humanSteroid 17-alpha-Hydroxylaseandrogenconformational changeconformational selectionCYP17A1cytochrome P450enzyme kineticsinduced-fit bindingP450 17A1pregnenolonepre-steady-state kineticssteroidsteroidogenesis

Identifiers

PMID31072872
PMCPMC6664176
OpenAlexW2944767593

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.