Evidence map›Paper›PMID 22383850›Full record

ArticleScience (New York, N.Y.)2012

Catalysis and sulfa drug resistance in dihydropteroate synthase.

Mi-Kyung Yun, Yinan Wu, Zhenmei Li, Ying Zhao, M Brett Waddell, Antonio M Ferreira, Richard E Lee, Donald Bashford, Stephen W White

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
4.8field-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

92 citing papers in PubMed, 247 citations in OpenAlex.

  1. Review
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  15. DynamicAmerican journal of respiratory and critical care medicine · 2025
    Observational
  16. Review
  17. Perturbation ofmBio · 2025
    Article
  18. Review
  19. Article
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32 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 1 country.

Mi-Kyung YunDepartment of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Yinan Wu
Zhenmei Li
Ying Zhao
M Brett Waddell
Antonio M Ferreira
Richard E Lee
Donald Bashford
Stephen W White
St. Jude Children's Research Hospital · USUniversity of Tennessee Health Science Center · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
Novel Inhibitors to DHPS to Probe Catalytic Mechanism & Therapeutic Potential - rR01AI070721 · NIAID · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI LEE, RICHARD E., WHITE, STEPHEN W · 2006 to 2015
$4.6M
NCI NIH HHS CA21765NCI NIH HHS P30 CA021765NIAID NIH HHS AI070721NIAID NIH HHS R01 AI070721
6 · The paper itself

Abstract

The sulfonamide antibiotics inhibit dihydropteroate synthase (DHPS), a key enzyme in the folate pathway of bacteria and primitive eukaryotes. However, resistance mutations have severely compromised the usefulness of these drugs. We report structural, computational, and mutagenesis studies on the catalytic and resistance mechanisms of DHPS. By performing the enzyme-catalyzed reaction in crystalline DHPS, we have structurally characterized key intermediates along the reaction pathway. Results support an S(N)1 reaction mechanism via formation of a novel cationic pterin intermediate. We also show that two conserved loops generate a substructure during catalysis that creates a specific binding pocket for p-aminobenzoic acid, one of the two DHPS substrates. This substructure, together with the pterin-binding pocket, explains the roles of the conserved active-site residues and reveals how sulfonamide resistance arises.

Indexed as

Drug Resistance, Bacterial4-Aminobenzoic AcidAmino Acid SequenceAnti-Bacterial AgentsBacillus anthracisBiocatalysisCatalytic DomainCrystallizationCrystallography, X-RayDihydropteroate SynthaseDiphosphatesMagnesiumModels, ChemicalModels, MolecularMolecular Sequence DataMutagenesis4-Aminobenzoic AcidAnti-Bacterial AgentsDihydropteroate SynthaseDiphosphatesdiphosphoric acidMagnesiumParabensSulfamethoxazoleSulfathiazoleSulfathiazoles

Identifiers

PMID22383850
PMCPMC3531234
OpenAlexW2133791017

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.