PMID: 9194167Apr 1, 1997Paper

Analysis of high-affinity binding determinants in the receptor binding epitope of basic fibroblast growth factor

Protein Engineering
H ZhuM E Wolff

Abstract

Basic fibroblast growth factor (bFGF) is implicated in the pathogenesis of several vascular and connective diseases. A key step in the discovery of bFGF receptor antagonists to mitigate these actions is to define the functional epitope required for receptor binding of the growth factor. In previous studies, we identified Glu96 as an essential residue in this epitope using site-directed mutagenesis. Here we examined the role of solvent accessible neighboring residues of Glu96 of bFGF on receptor binding affinity. Wild-type bFGF and its muteins were cloned and expressed in Escherichia coli and evaluated for FGF receptor binding affinity. Replacement of Asn104 of bFGF by alanine reduced receptor binding affinity over 400-fold compared with wild-type bFGF. We next explored the effect of neighboring residues of Asn104 on receptor binding affinity-Muteins in which Arg97, Leu98, Glu99, Asn101, Asn102, Thr105 and Pro141 were individually replaced by alanine exhibited receptor binding similar to wild-type bFGF. By contrast, substitution of Tyr103 or Leu140 by alanine reduced receptor binding affinity about 400- and 150-fold, respectively, in accord with a previous report. We conclude that at least six solvent-accessible residues in bFGF...Continue Reading

Citations

Sep 29, 1998·The European Journal of Neuroscience·J M GreeneR F Alderson
Apr 29, 2008·The Journal of Biological Chemistry·Seiji MoriYoshikazu Takada
Feb 23, 2008·Critical Reviews in Clinical Laboratory Sciences·Malgorzata ZakrzewskaAntoni Wiedlocha
Dec 20, 2007·Oral and Maxillofacial Surgery Clinics of North America·Jonathan A Britto
Sep 18, 1999·Cell·A N PlotnikovM Mohammadi
Jun 22, 2002·The Journal of Biological Chemistry·Britt-Marie Loo, Markku Salmivirta
Jun 20, 2003·The Journal of Biological Chemistry·Shaun K OlsenMoosa Mohammadi
Sep 13, 2000·The Journal of Biological Chemistry·Y ChiC Yu

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