Evidence map›Paper›PMID 25079510›Full record

ArticleACS chemical biology2014

Structure-guided functional characterization of enediyne self-sacrifice resistance proteins, CalU16 and CalU19.

Sherif I Elshahawi, Theresa A Ramelot, Jayaraman Seetharaman, Jing Chen, Shanteri Singh, Yunhuang Yang, Kari Pederson, Madan K Kharel, Rong Xiao, Scott Lew and 10 more

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

17 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Promiscuous Enzymes for Residue-Specific Peptide and Protein Late-Stage Functionalization.Chembiochem : a European journal of chemical biology · 2023
    Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. The crystal structure of DynF from the dynemicin-biosynthesis pathway of Micromonospora chersina.Acta crystallographica. Section F, Structural biology communications · 2022
    Article
  9. Structural characterization of DynU16, a START/Bet v1-like protein involved in dynemicin biosynthesis.Acta crystallographica. Section F, Structural biology communications · 2021
    Article
  10. Review
  11. Crossroads of Antibiotic Resistance and Biosynthesis.Journal of molecular biology · 2019
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. A community resource of experimental data for NMR / X-ray crystal structure pairs.Protein science : a publication of the Protein Society · 2016
    Review
  17. Review
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

20 authors at 8 institutions in 1 country.

Sherif I ElshahawiDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky , Lexington, Kentucky 40536, United States.
Theresa A Ramelot
Jayaraman Seetharaman
Jing Chen
Shanteri Singh
Yunhuang Yang
Kari Pederson
Madan K Kharel
Rong Xiao
Scott Lew
Ragothaman M Yennamalli
Mitchell D Miller
Fengbin Wang
Liang Tong
Gaetano T Montelione
Michael A Kennedy
Craig A Bingman
Haining Zhu
George N Phillips
Jon S Thorson
University of Kentucky · USRice University · USMiami University · USNew York Structural Biology Center · USRutgers, The State University of New Jersey · USColumbia University · USUniversity of Georgia · USUniversity of Wisconsin–Madison · US

Funding

University of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI Jennifer F Rogers · 2013 to 2026
$38.3M
University of Georgia ProjectU54GM094597 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI MONTELIONE, GAETANO T · 2010 to 2014
$36.9M
Kentucky Center for Clinical and Translational ScienceUL1TR000117 · NCATS · UNIVERSITY OF KENTUCKY · PI KERN, PHILIP A · 2012 to 2015
$13.3M
Center for Biomedical Research Excellence in the Molecular Basis of Human DiseaseP20GM103486 · NIGMS · UNIVERSITY OF KENTUCKY · PI LOUIS HERSH, LOUIS HERSH LOUIS HERSH · 2012 to 2013
$4.2M
STUDIES ON CALICHEAMICIN BIOSYNTHESIS AND SELF RESISTANCER01CA084374 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI THORSON, JON SCOTT · 2000 to 2013
$3.6M
Enzyme Discovery for Natural Product BiosynthesisU01GM098248 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI PHILLIPS, GEORGE NEAL · 2011 to 2015
$2.8M
LTQ Orbitrap XL ETD mass spectrometerS10RR029127 · NCRR · UNIVERSITY OF KENTUCKY · PI ZHU, HAINING · 2010 to 2010
$908k
NCATS NIH HHS UL1 TR000117NCATS NIH HHS UL1TR000117NCI NIH HHS CA84374NCI NIH HHS P30 CA177558NCI NIH HHS P30CA177558NCI NIH HHS R01 CA084374NCRR NIH HHS 1S10RR029127NCRR NIH HHS S10 RR029127NIGMS NIH HHS P20 GM103486NIGMS NIH HHS P20GM103486NIGMS NIH HHS U01 GM098248NIGMS NIH HHS U01GM098248NIGMS NIH HHS U54 GM094597NIGMS NIH HHS U54-GM094597
6 · The paper itself

Abstract

Calicheamicin γ1I (1) is an enediyne antitumor compound produced by Micromonospora echinospora spp. calichensis, and its biosynthetic gene cluster has been previously reported. Despite extensive analysis and biochemical study, several genes in the biosynthetic gene cluster of 1 remain functionally unassigned. Using a structural genomics approach and biochemical characterization, two proteins encoded by genes from the 1 biosynthetic gene cluster assigned as "unknowns", CalU16 and CalU19, were characterized. Structure analysis revealed that they possess the STeroidogenic Acute Regulatory protein related lipid Transfer (START) domain known mainly to bind and transport lipids and previously identified as the structural signature of the enediyne self-resistance protein CalC. Subsequent study revealed calU16 and calU19 to confer resistance to 1, and reminiscent of the prototype CalC, both CalU16 and CalU19 were cleaved by 1 in vitro. Through site-directed mutagenesis and mass spectrometry, we identified the site of cleavage in each protein and characterized their function in conferring resistance against 1. This report emphasizes the importance of structural genomics as a powerful tool for the functional annotation of unknown proteins.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsCrystallography, X-RayDrug Resistance, BacterialEnediynesGenomicsLipidsMicromonosporaModels, MolecularMolecular StructureMultigene FamilyMutagenesis, Site-DirectedMutationProtein Structure, TertiarySpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationAnti-Bacterial AgentsBacterial ProteinsEnediynesLipids

Identifiers

PMID25079510
PMCPMC4201346
OpenAlexW2084209792

What OpenQuestion holds

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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.