Evidence map›Paper›PMID 39639052›Full record

ArticleCommunications biology2024

Exquisite selectivity of griselimycin extends to beta subunit of DNA polymerases from Gram-negative bacterial pathogens.

Michael K Fenwick, Phillip G Pierce, Jan Abendroth, Kayleigh F Barrett, Lynn K Barrett, Kalinga Bowatte, Ryan Choi, Ian Chun, Deborah G Conrady, Justin K Craig and 23 more

Abstract read
In one paragraph

Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

33 authors.

Michael K Fenwick *Seattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.ORCID 0000-0001-5066-4962
Phillip G Pierce *Seattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.ORCID 0000-0002-8176-770X
Jan AbendrothSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Kayleigh F BarrettSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Lynn K BarrettSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Kalinga BowatteSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Ryan ChoiSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Ian ChunSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Deborah G ConradySeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Justin K CraigSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
David M DranowSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Bradley HammersonSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Tate HigginsSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Donald D LorimerSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Peer LukatStructure and Function of Proteins, Helmholtz Center for Infection Research, Inhoffenstraße 7, 38124, Braunschweig, Germany.
Stephen J MayclinSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Stephen Nakazawa HewittSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Ying Po PengSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.ORCID 0000-0001-7165-6021
Ashwini ShanbhogueSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Hayden SmutneySeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Matthew Z Z StiglianoSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.ORCID 0009-0000-6673-6713
Logan M TillerySeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.ORCID 0000-0002-5431-3489
Hannah S UdellSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Ellen G WallaceSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.ORCID 0009-0007-0149-7417
Amy E DeRocherSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.ORCID 0000-0003-1205-7920
Isabelle Q PhanSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.ORCID 0000-0001-6873-3401
Bart L StakerSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.ORCID 0000-0001-9570-5086
Sandhya SubramanianSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Wesley C Van VoorhisSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA.
Wulf BlankenfeldtStructure and Function of Proteins, Helmholtz Center for Infection Research, Inhoffenstraße 7, 38124, Braunschweig, Germany.ORCID 0000-0001-9886-9668
Rolf MüllerDepartment of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), 66123, Saarbrücken, Germany. rolf.mueller@helmholtz.hzi.de.ORCID 0000-0002-1042-5665
Thomas E EdwardsSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA. tom.edwards@ucb.com.ORCID 0000-0002-0474-8003
Peter J MylerSeattle Structural Genomics Center for Infectious Disease, 307 Westlake Avenue North, Seattle, WA, 98109, USA. Peter.Myler@seattlechildrens.org.ORCID 0000-0002-0056-0513

Funding

User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Gregory L Hura · 2017 to 2026
$28.6M
Centers for Research on Structural Biology of Infectious Diseases: Universal Influenza Vaccine Research75N93022C00036 · NIAID · SEATTLE CHILDREN'S HOSPITAL · PI STAKER, BART · 2022 to 2025
$21.7M
Michigan Economic Development Corporation (MEDC) 085P1000817NIAID NIH HHS 75N93022C00036NIAID NIH HHS HHSN272201700059CNIGMS NIH HHS P30 GM124169U.S. Department of Energy (DOE) DE-AC02-05CH11231U.S. Department of Energy (DOE) DE-AC02-06CH11357U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) P30 GM124169-01
6 · The paper itself

Abstract

Griselimycin, a cyclic depsidecapeptide produced by Streptomyces griseus, is a promising lead inhibitor of the sliding clamp component of bacterial DNA polymerases (β-subunit of Escherichia coli DNA pol III). It was previously shown to inhibit the Mycobacterium tuberculosis β-clamp with remarkably high affinity and selectivity - the peptide lacks any interaction with the human sliding clamp. Here, we used a structural genomics approach to address the prospect of broader-spectrum inhibition, in particular of β-clamps from Gram-negative bacterial targets. Fifteen crystal structures of β-clamp orthologs were solved, most from Gram-negative bacteria, including eight cocrystal structures with griselimycin. The ensemble of structures samples widely diverse β-clamp architectures and reveals unique protein-ligand interactions with varying degrees of complementarity. Although griselimycin clearly co-evolved with Gram-positive β-clamps, binding affinity measurements demonstrate that the high selectivity observed previously extends to the Gram-negative orthologs, with K

Indexed as

DNA Polymerase IIIAnti-Bacterial AgentsBacterial ProteinsCrystallography, X-RayGram-Negative BacteriaModels, MolecularAnti-Bacterial AgentsBacterial Proteinsbeta subunit, DNA polymerase IIIDNA Polymerase III

Identifiers

PMID39639052
PMCPMC11621423

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.