Evidence map›Paper›PMID 22432862›Full record

ArticleBiochemistry2012

Insight into the molecular basis of aromatic polyketide cyclization: crystal structure and in vitro characterization of WhiE-ORFVI.

Ming-Yue Lee, Brian D Ames, Shiou-Chuan Tsai

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 21% 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

13 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Understanding the Enzyme (Journal of chemical information and modeling · 2024
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  5. Structural characterization of DynU16, a START/Bet v1-like protein involved in dynemicin biosynthesis.Acta crystallographica. Section F, Structural biology communications · 2021
    Article
  6. Review
  7. Article
  8. Article
  9. An unusual intramolecularTetrahedron · 2016
    Article
  10. Structural and functional analysis of two di-domain aromatase/cyclases from type II polyketide synthases.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  11. Article
  12. Article
  13. Rational reprogramming of fungal polyketide first-ring cyclization.Proceedings of the National Academy of Sciences of the United States of America · 2013
    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.

Ming-Yue LeeDepartment of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA.
Brian D Ames
Shiou-Chuan Tsai
University of California, Irvine · US

Funding

The Molecular Basis of Regio-Specificity in Fungal Polyketide SynthaseR01GM100305 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI BURKART, MICHAEL D., TSAI, SHIOU-CHUAN · 2012 to 2015
$1.6M
The Ketoreduction and Cyclization of Aromatic Polyketide BiosynthesisR01GM076330 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI TSAI, SHIOU-CHUAN · 2007 to 2011
$1.3M
NIGMS NIH HHS R01 GM076330NIGMS NIH HHS R01GM076330NIGMS NIH HHS R01 GM100305
6 · The paper itself

Abstract

Aromatic polyketides are biologically active natural products. Many important pharmaceuticals are derived from aromatic polyketides. Especially important in aromatic polyketide biosynthesis is the regiospecific cyclization of a linear, preassembled polyketide chain catalyzed by aromatase/cyclase (ARO/CYC), which serves as a key control point in aromatic ring formation. How different ARO/CYCs promote different cyclization patterns is not well understood. The whiE locus of Streptomyces coelicolor A3(2) is responsible for the biosynthesis of an aromatic polyketide precursor to the gray spore pigment. The WhiE ARO/CYC catalyzes the regiospecific C9-C14 and C7-C16 cyclization and aromatization of a 24-carbon polyketide chain. WhiE ARO/CYC shares a high degree of similarity to another nonreducing PKS ARO/CYC, TcmN ARO/CYC. This paper presents the apo crystal structure of WhiE ARO/CYC, and cocrystal structures of WhiE and TcmN ARO/CYCs bound with polycyclic aromatic compounds that mimic the respective ARO/CYC products. Site-directed mutagenesis coupled with in vitro PKS reconstitution assays was used to characterize the interior pocket residues of WhiE ARO/CYC. The results confirmed that the interior pocket of ARO/CYCs is a critical determinant of polyketide cyclization specificity. A unified ARO/CYC-mediated cyclization mechanism is proposed on the basis of these structural and functional results.

Indexed as

Amino Acid SequenceAromataseBacterial ProteinsCrystallography, X-RayCyclizationModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedPolyketidesPolyketide SynthasesProtein ConformationSequence AlignmentStreptomyces coelicolorAromataseBacterial ProteinsPolyketidesPolyketide Synthases

Identifiers

PMID22432862
PMCPMC3339804
OpenAlexW2084370505

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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.