Evidence map›Paper›PMID 30257866›Full record

ArticleThe Journal of biological chemistry2018

Structural basis, stoichiometry, and thermodynamics of binding of the chemokines KC and MIP2 to the glycosaminoglycan heparin.

Krishna Mohan Sepuru, Balaji Nagarajan, Umesh R Desai, Krishna Rajarathnam

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2018. 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
1.4field-weighted citation impact, top 15% 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
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  4. Article
  5. Solvent Model Benchmark for Molecular Dynamics of Glycosaminoglycans.Journal of chemical information and modeling · 2023
    Article
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  8. Article
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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

4 authors at 3 institutions in 2 countries.

Krishna Mohan SepuruFrom the Departments of Biochemistry and Molecular Biology; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555.
Balaji NagarajanDepartment of Medicinal Chemistry and Institute for Structural Biology, and Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia 23219.
Umesh R DesaiDepartment of Medicinal Chemistry and Institute for Structural Biology, and Drug Discovery and Development, Virginia Commonwealth University, Richmond, Virginia 23219.
Krishna RajarathnamFrom the Departments of Biochemistry and Molecular Biology; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas 77555; Microbiology and Immunology. Electronic address: krrajara@utmb.edu.
Virginia Commonwealth University · USBipar · FRThe University of Texas Medical Branch at Galveston · US

Funding

Therapeutic assessment of synthetic heparin sulfates in transplantation modelsP01HL107152 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DESAI, UMESH RAMANLAL · 2011 to 2017
$15.8M
Chemokine Synergy and Neutrophil FunctionR21AI124681 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI RAJARATHNAM, KRISHNA · 2016 to 2017
$426k
Malvern MicroCal PEAQ Isothermal Titration CalorimeterS10OD023576 · OD · UNIVERSITY OF TEXAS MED BR GALVESTON · PI RAJARATHNAM, KRISHNA · 2017 to 2017
$120k
NHLBI NIH HHS P01 HL107152NIAID NIH HHS R21 AI124681NIH HHS S10 OD023576
6 · The paper itself

Abstract

Keratinocyte-derived chemokine (KC or mCXCL1) and macrophage inflammatory protein 2 (MIP2 or mCXCL2) play nonredundant roles in trafficking blood neutrophils to sites of infection and injury. The functional responses of KC and MIP2 are intimately coupled to their interactions with glycosaminoglycans (GAGs). GAG interactions orchestrate chemokine concentration gradients and modulate receptor activity, which together regulate neutrophil trafficking. Here, using NMR, molecular dynamics (MD) simulations, and isothermal titration calorimetry (ITC), we characterized the molecular basis of KC and MIP2 binding to the GAG heparin. Both chemokines reversibly exist as monomers and dimers, and the NMR analysis indicates that the dimer binds heparin with higher affinity. The ITC experiments indicate a stoichiometry of two GAGs per KC or MIP2 dimer and that the enthalpic and entropic contributions vary significantly between the two chemokine-heparin complexes. NMR-based structural models of heparin-KC and heparin-MIP2 complexes reveal that different combinations of residues from the N-loop, 40s turn, β

Indexed as

AnimalsBinding SitesCalorimetryChemokine CXCL1Chemokine CXCL2HeparinHydrogen BondingMiceMolecular Dynamics SimulationProtein BindingThermodynamicsChemokine CXCL1Chemokine CXCL2Cxcl1 protein, mouseCxcl2 protein, mouseHeparinchemokineglycosaminoglycanheparinisothermal titration calorimetry (ITC)molecular dynamicsnuclear magnetic resonance (NMR)

Identifiers

PMID30257866
PMCPMC6240865
OpenAlexW2894134508

What OpenQuestion holds

Textmetadata
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.