Evidence map›Paper›PMID 40086440›Full record

ArticleStructure (London, England : 1993)2025

Structure of a putative terminal amidation domain in natural product biosynthesis.

Michael R Rankin, Dheeraj Khare, Lena Gerwick, David H Sherman, William H Gerwick, Janet L Smith

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Structure (London, England : 1993), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Michael R RankinLife Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Dheeraj KhareLife Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USA.
Lena GerwickCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA.
David H ShermanLife Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USA; Departments of Medicinal Chemistry, Chemistry, and Microbiology & Immunology, University of Michigan, Ann Arbor, MI 48109, USA.
William H GerwickCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92039, USA.
Janet L SmithLife Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: janetsmith@umich.edu.

Funding

User Training & OutreachP30GM138396 · NIGMS · UCHICAGO ARGONNE, LLC · PI JANET L. SMITH · 2020 to 2026
$34.3M
Unified Computation Tools for Natural Products ResearchR01GM107550 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COTTRELL, GARRISON W, GERWICK, WILLIAM HENRY · 2013 to 2025
$8.2M
STRUCTURE AND FUNCTION OF A PURINE BIOSYNTHETIC ENZYMER01DK042303 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SMITH, JANET L. · 1990 to 2024
$6.6M
Discovery and Characterization of Natural Product Systems-Research Supplement to Promote DiversityR35GM118101 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHERMAN, DAVID H · 2016 to 2025
$3.3M
Cellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6M
Structural Biology of Complex EnzymesR01GM161002 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SMITH, JANET L. · 2025 to 2025
$785k
Expanding the Library of (Un)Natural Products through Megasynthase Docking Domain EngineeringF31CA265082 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RANKIN, MICHAEL RAYMOND · 2021 to 2023
$117k
NCI NIH HHS F31 CA265082NIDDK NIH HHS R01 DK042303NIGMS NIH HHS P30 GM138396NIGMS NIH HHS R01 GM107550NIGMS NIH HHS R01 GM161002NIGMS NIH HHS R35 GM118101NIGMS NIH HHS T32 GM145304
6 · The paper itself

Abstract

Bacteria are rich sources of pharmaceutically valuable natural products, many crafted by modular polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). PKS and NRPS systems typically contain a thioesterase (TE) to offload a linear or cyclized product from a carrier protein, but alternative chemistry is needed for products with a terminal amide. Several pathways with amidated products also possess an uncharacterized 400-amino acid terminal domain. We present the characterization and structure of this putative terminal amidation domain (TAD). TAD binds NAD with the nicotinamide near an invariant cysteine that is also accessible to an intermediate on a carrier protein, indicating a catalytic role. The TAD structure resembles cyanobacterial acyl-ACP reductase (AAR), which binds NADPH near an analogous catalytic cysteine. Bioinformatic analysis reveals that TADs are broadly distributed across bacterial phyla and often occur at the end of terminal NRPS modules, suggesting many amidated products may yet be discovered.

Indexed as

Bacterial ProteinsBiological ProductsPeptide SynthasesPolyketide SynthasesAmino Acid SequenceCrystallography, X-RayCysteineModels, MolecularNADNADPProtein BindingProtein DomainsBacterial ProteinsBiological ProductsCysteineNADNADPnon-ribosomal peptide synthasePeptide SynthasesPolyketide Synthasesbiosynthesiscrosslinkingcrystallographygenome miningmass spectrometrynatural products

Identifiers

PMID40086440
PMCPMC12048289

What OpenQuestion holds

Textmetadata
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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.