Evidence map›Paper›PMID 22579249›Full record

ArticleStructure (London, England : 1993)2012

Staphylococcus aureus FabI: inhibition, substrate recognition, and potential implications for in vivo essentiality.

Johannes Schiebel, Andrew Chang, Hao Lu, Michael V Baxter, Peter J Tonge, Caroline Kisker

Open access · bronzeAbstract read
In one paragraph

Article in Structure (London, England : 1993), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

46 citing papers in PubMed, 91 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Hidden Interactions: Quantum Perspectives in Drug Design.Methods in molecular biology (Clifton, N.J.) · 2026
    Review
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  7. Article
  8. Article
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  11. Article
  12. Review
  13. Article
  14. Article
  15. The Complex Diseases ofVeterinary sciences · 2021
    Review
  16. Article
  17. Article
  18. Review
  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

6 authors at 2 institutions in 2 countries.

Johannes SchiebelRudolf Virchow Center for Experimental Biomedicine, Institute for Structural Biology, University of Würzburg, D-97080 Würzburg, Germany.
Andrew Chang
Hao Lu
Michael V Baxter
Peter J Tonge
Caroline Kisker
Stony Brook University · USUniversity of Würzburg · DE

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008444 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI FROHMAN, MICHAEL A. · 1992 to 2024
$12.6M
Chemotherapeutics Against Multi-Drug Resistant TuberculosisU01AI070383 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI TONGE, PETER J · 2006 to 2010
$3.4M
Mechanism of Slow Onset Enzyme Inhibition and Translation to Time-Dependent Drug ActivityR01GM102864 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI TONGE, PETER J · 2012 to 2021
$2.6M
Targetting InhA For Anti-TB Drug DiscoveryR01AI044639 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI TONGE, PETER J · 1999 to 2009
$1.9M
SBU Chemistry-Biology Interface Training ProgramT32GM092714 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI SAMPSON, NICOLE S, TONGE, PETER J · 2010 to 2019
$1.7M
Inhibition of Fatty Acid Biosynthesis in M. TuberculosisR21AI044639 · NIAID · STATE UNIVERSITY NEW YORK STONY BROOK · PI TONGE, PETER J · 2003 to 2003
$252k
NIAID NIH HHS R01 AI044639NIAID NIH HHS R21 AI044639NIAID NIH HHS U01 AI070383NIGMS NIH HHS R01 GM102864NIGMS NIH HHS T32 GM008444NIGMS NIH HHS T32GM008444NIGMS NIH HHS T32 GM092714NIGMS NIH HHS T32GM092714
6 · The paper itself

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infections constitute a serious health threat worldwide, and novel antibiotics are therefore urgently needed. The enoyl-ACP reductase (saFabI) is essential for the S. aureus fatty acid biosynthesis and, hence, serves as an attractive drug target. We have obtained a series of snapshots of this enzyme that provide a mechanistic picture of ligand and inhibitor binding, including a dimer-tetramer transition combined with extensive conformational changes. Significantly, our results reveal key differences in ligand binding and recognition compared to orthologous proteins. The remarkable observed protein flexibility rationalizes our finding that saFabI is capable of efficiently reducing branched-chain fatty acid precursors. Importantly, branched-chain fatty acids represent a major fraction of the S. aureus cell membrane and are crucial for its in vivo fitness. Our discovery thus addresses a long-standing controversy regarding the essentiality of the fatty acid biosynthesis pathway in S. aureus rationalizing saFabI as a drug target.

Indexed as

Amino Acid SequenceBacterial ProteinsEnoyl-(Acyl-Carrier-Protein) Reductase (NADH)Fatty AcidsKineticsLigandsMolecular Sequence DataProtein ConformationStaphylococcus aureusStructure-Activity RelationshipSubstrate SpecificityBacterial ProteinsEnoyl-(Acyl-Carrier-Protein) Reductase (NADH)Fatty AcidsLigands

Identifiers

PMID22579249
PMCPMC3376755
OpenAlexW2023232635

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.