Evidence map›Paper›PMID 34735239›Full record

ArticleScience (New York, N.Y.)2021

Mapping the catalytic conformations of an assembly-line polyketide synthase module.

Dillon P Cogan, Kaiming Zhang, Xiuyuan Li, Shanshan Li, Grigore D Pintilie, Soung-Hun Roh, Charles S Craik, Wah Chiu, Chaitan Khosla

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
–field-weighted citation impact
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

44 citing papers in PubMed.

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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.

Dillon P Cogan *Department of Chemistry, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0003-4563-2397
Kaiming Zhang *Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0003-0414-4776
Xiuyuan LiDepartment of Chemistry, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-3970-8183
Shanshan LiDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-7041-5960
Grigore D PintilieDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Soung-Hun RohDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0003-3851-7200
Charles S CraikDepartment of Pharmaceutical Chemistry, University of California-San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0001-7704-9185
Wah ChiuDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-8910-3078
Chaitan KhoslaDepartment of Chemistry, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0001-6529-495X

Funding

The Stanford-SLAC CryoEM Center supplementU24GM129541 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH, HEDMAN, BRITT · 2018 to 2023
$54.8M
3 D ELECTRON MICROSCOPY OF MACROMOLECULES (5P41RR002250-27)P41GM103832 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH · 2012 to 2019
$15.1M
Unified Data Resource for Large Complexes Determined by Cryo-Electron MicroscopyR01GM079429 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH · 2007 to 2021
$11.6M
Structure, Mechanism, and Engineering of Assembly Line Polyketide SynthasesR01GM087934 · NIGMS · STANFORD UNIVERSITY · PI KHOSLA, CHAITAN · 2009 to 2021
$4.9M
Mechanisms and Evolution of Assembly-Line Polyketide SynthasesR35GM141799 · NIGMS · STANFORD UNIVERSITY · PI CHAITAN KHOSLA · 2021 to 2026
$2.5M
Acquisition of a 300 kV Electron Microscope for Structural BiologyS10OD021600 · OD · STANFORD UNIVERSITY · PI CHIU, WAH · 2016 to 2016
$2.0M
Mechanistic Studies of Polyketide Synthases Enabled by Unnatural Amino Acids and Antibody Fragment Structural ToolsF32GM136039 · NIGMS · STANFORD UNIVERSITY · PI COGAN, DILLON P · 2020 to 2022
$196k
NIGMS NIH HHS F32 GM136039NIGMS NIH HHS P41 GM103832NIGMS NIH HHS R01 GM079429NIGMS NIH HHS R01 GM087934NIGMS NIH HHS R35 GM141799NIGMS NIH HHS U24 GM129541NIH HHS S10 OD021600
6 · The paper itself

Abstract

Assembly-line polyketide synthases, such as the 6-deoxyerythronolide B synthase (DEBS), are large enzyme factories prized for their ability to produce specific and complex polyketide products. By channeling protein-tethered substrates across multiple active sites in a defined linear sequence, these enzymes facilitate programmed small-molecule syntheses that could theoretically be harnessed to access countless polyketide product structures. Using cryogenic electron microscopy to study DEBS module 1, we present a structural model describing this substrate-channeling phenomenon. Our 3.2- to 4.3-angstrom-resolution structures of the intact module reveal key domain-domain interfaces and highlight an unexpected module asymmetry. We also present the structure of a product-bound module that shines light on a recently described “turnstile” mechanism for transient gating of active sites along the assembly line.

Indexed as

BiocatalysisCatalytic DomainCryoelectron MicroscopyModels, MolecularPolyketide SynthasesProtein ConformationProtein DomainsSaccharopolysporaPolyketide Synthases

Identifiers

PMID34735239
PMCPMC8842837

What OpenQuestion holds

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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.