Evidence map›Paper›PMID 31982812›Full record

ArticleJournal of inorganic biochemistry2020

Multiple drug binding modes in Mycobacterium tuberculosis CYP51B1.

Molly M Lockart, Joseph T Butler, Carson J Mize, Morgan N Fair, Alex A Cruce, Kip P Conner, William M Atkins, Michael K Bowman

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of inorganic biochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 48% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

8 authors at 2 institutions in 1 country.

Molly M LockartDepartment of Chemistry, Box 870336, University of Alabama, Tuscaloosa, AL 35487-0336, United States of America. Electronic address: mmlockart@ua.edu.
Joseph T ButlerDepartment of Chemistry, Box 870336, University of Alabama, Tuscaloosa, AL 35487-0336, United States of America.
Carson J MizeDepartment of Chemistry, Box 870336, University of Alabama, Tuscaloosa, AL 35487-0336, United States of America.
Morgan N FairDepartment of Chemistry, Box 870336, University of Alabama, Tuscaloosa, AL 35487-0336, United States of America.
Alex A CruceDepartment of Chemistry, Box 870336, University of Alabama, Tuscaloosa, AL 35487-0336, United States of America.
Kip P ConnerDepartment of Medicinal Chemistry, Box 357610, University of Washington, Seattle, WA 98195-7610, United States of America.
William M AtkinsDepartment of Medicinal Chemistry, Box 357610, University of Washington, Seattle, WA 98195-7610, United States of America.
Michael K BowmanDepartment of Chemistry, Box 870336, University of Alabama, Tuscaloosa, AL 35487-0336, United States of America.
University of Alabama · USUniversity of Washington · US

Funding

Pharmacological Sciences SupplementT32GM007750 · NIGMS · UNIVERSITY OF WASHINGTON · PI ATKINS, WILLIAM M · 1985 to 2023
$12.6M
Functional Dynamics of Cytochrome P4503A4R01GM130810 · NIGMS · UNIVERSITY OF WASHINGTON · PI ATKINS, WILLIAM M · 2018 to 2021
$1.8M
NIGMS NIH HHS R01 GM130810NIGMS NIH HHS T32 GM007750
6 · The paper itself

Abstract

The Mycobacterium tuberculosis (Mtb) genome encodes 20 different cytochrome P450 enzymes (CYPs), many of which serve essential biosynthetic roles. CYP51B1, the Mtb version of eukaryotic sterol demethylase, remains a potential therapeutic target. The binding of three drug fragments containing nitrogen heterocycles to CYP51B1 is studied here by continuous wave (CW) and pulsed electron paramagnetic resonance (EPR) techniques to determine how each drug fragment binds to the heme active-site. All three drug fragments form a mixture of complexes, some of which retain the axial water ligand from the resting state. Hyperfine sublevel correlation spectroscopy (HYSCORE) and electron-nuclear double resonance spectroscopy (ENDOR) observe protons of the axial water and on the drug fragments that reveal drug binding modes. Binding in CYP51B1 is complicated by the presence of multiple binding modes that coexist in the same solution. These results aid our understanding of CYP-inhibitor interactions and will help guide future inhibitor design.

Indexed as

Bacterial ProteinsCytochrome P-450 Enzyme SystemAnti-Bacterial AgentsCatalytic DomainCytochrome P-450 Enzyme InhibitorsMycobacterium tuberculosisAnti-Bacterial AgentsBacterial Proteinscytochrome P-450 CYP51, Mycobacterium tuberculosisCytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemCytochrome P450EPRHYSCOREMycobacterium tuberculosis

Identifiers

PMID31982812
PMCPMC7092363
OpenAlexW3000328671

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.