Evidence map›Paper›PMID 30031837›Full record

ArticleArchives of biochemistry and biophysics2018

Probing the role of proline -135 on the structure, stability, and cell proliferation activity of human acidic fibroblast growth factor.

Julie Eberle Davis, Arwa Alghanmi, Ravi Kumar Gundampati, Srinivas Jayanthi, Ellen Fields, Monica Armstrong, Vanessa Weidling, Varun Shah, Shilpi Agrawal, Bhanu Prasanth Koppolu and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Archives of biochemistry and biophysics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 40% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Phenotypic Robustness of Epidermal Stem Cell Number inFrontiers in cell and developmental biology · 2021
    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

12 authors at 2 institutions in 1 country.

Julie Eberle DavisDepartment of Chemistry and Biochemistry, University of Arkansas, 1 University of Arkansas, Fayetteville, AR, 72701, USA.
Arwa AlghanmiDepartment of Chemistry and Biochemistry, University of Arkansas, 1 University of Arkansas, Fayetteville, AR, 72701, USA.
Ravi Kumar GundampatiDepartment of Chemistry and Biochemistry, University of Arkansas, 1 University of Arkansas, Fayetteville, AR, 72701, USA.
Srinivas JayanthiDepartment of Chemistry and Biochemistry, University of Arkansas, 1 University of Arkansas, Fayetteville, AR, 72701, USA.
Ellen FieldsDepartment of Chemistry and Biochemistry, University of Arkansas, 1 University of Arkansas, Fayetteville, AR, 72701, USA.
Monica ArmstrongDepartment of Chemistry and Biochemistry, University of Arkansas, 1 University of Arkansas, Fayetteville, AR, 72701, USA.
Vanessa WeidlingDepartment of Chemistry and Biochemistry, University of Arkansas, 1 University of Arkansas, Fayetteville, AR, 72701, USA.
Varun ShahDepartment of Chemistry and Biochemistry, University of Arkansas, 1 University of Arkansas, Fayetteville, AR, 72701, USA.
Shilpi AgrawalDepartment of Chemistry and Biochemistry, University of Arkansas, 1 University of Arkansas, Fayetteville, AR, 72701, USA.
Bhanu Prasanth KoppoluJoint Department of Biomedical Engineering, North Carolina State University and University of North Carolina-Chapel Hill, Raleigh, NC, 27695, USA.
David A ZaharoffJoint Department of Biomedical Engineering, North Carolina State University and University of North Carolina-Chapel Hill, Raleigh, NC, 27695, USA.
Thallapuranam Krishnaswamy Suresh KumarDepartment of Chemistry and Biochemistry, University of Arkansas, 1 University of Arkansas, Fayetteville, AR, 72701, USA. Electronic address: sthalla@uark.edu.
University of Arkansas at Fayetteville · USNorth Carolina State University · US

Funding

Structure based drug discoveryP20RR015569 · NCRR · UNIVERSITY OF ARKANSAS AT FAYETTEVILLE · PI MILLETT, FRANCIS S · 2000 to 2009
$21.4M
Center for Protein Structure and FunctionP30GM103450 · NIGMS · UNIVERSITY OF ARKANSAS AT FAYETTEVILLE · PI MILLETT, FRANCIS S · 2012 to 2014
$3.2M
Biopolymer-based strategies for local delivery of cytokine therapeuticsR01CA172631 · NCI · UNIVERSITY OF ARKANSAS AT FAYETTEVILLE · PI ZAHAROFF, DAVID · 2014 to 2018
$1.5M
NCI NIH HHS R01 CA172631NCRR NIH HHS P20 RR015569NIGMS NIH HHS P30 GM103450
6 · The paper itself

Abstract

Human acidic fibroblast growth factor 1 (hFGF1) is a protein intricately involved in cell growth and tissue repair. In this study, we investigate the effect(s) of understanding the role of a conserved proline (P135), located in the heparin binding pocket, on the structure, stability, heparin binding affinity, and cell proliferation activity of hFGF1. Substitution of proline-135 with a positively charged lysine (P135K) resulted in partial destabilization of the protein; however, the overall structural integrity of the protein was maintained upon substitution of proline-135 with either a negative charge (P135E) or a polar amino acid (P135Q). Interestingly, upon heparin binding, an increase in thermal stability equivalent to that of wt-hFGF1 was observed when P135 was replaced with a positive (P135K) or a negative charge (P135E), or with a polar amino acid (P135Q). Surprisingly, introduction of negative charge in the heparin-binding pocket at position 135 (P135E) increased hFGF1's affinity for heparin by 3-fold, while the P135K mutation, did not alter the heparin-binding affinity. However, the enhanced heparin-binding affinity of mutant P135E did not translate to an increase in cell proliferation activity. Interestingly, the P135K and P135E double mutations, P135K/R136E and P135/R136E, reduced the heparin binding affinity by ∼3-fold. Furthermore, the cell proliferation activity was increased when the charge reversal mutation R136E was paired with both P135E (P135E/R136E) and P135K (P135K/R136E). Overall, the results of this study suggest that while heparin is useful for stabilizing hFGF1 on the cell surface, this interaction is not mandatory for activation of the FGF receptor.

Indexed as

Cell ProliferationFibroblast Growth Factor 1HeparinHumansMutagenesis, Site-DirectedProlineProtein BindingProtein StabilityProtein Structure, TertiaryProton Magnetic Resonance SpectroscopyReceptors, Fibroblast Growth FactorFibroblast Growth Factor 1HeparinProlineReceptors, Fibroblast Growth FactorBioactivityCharge-reversalFibroblast growth factorHeparin bindingStability

Identifiers

PMID30031837
PMCPMC6152824
OpenAlexW2884280840

What OpenQuestion holds

Textmetadata
LicenceTDM
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.