Molecular mechanism of inhibition of nonclassical FGF-1 export.

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Rajalingam D, Kumar TK, Soldi R, Graziani I, Prudovsky I, Yu C

Molecular mechanism of inhibition of nonclassical FGF-1 export.

Biochemistry. 2005 Nov 29;44(47):15472-9.

PubMed ID

16300395 [ View in PubMed

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Abstract

Fibroblast growth factor (FGF-1) lacks a signal sequence and is exported by an unconventional release mechanism. The nonclassical export of FGF-1 has been shown to be inhibited by an anti-allergic and anti-inflammatory drug, amlexanox (AMX). We investigate the molecular mechanism(s) underlying the inhibitory action of AMX on the release of FGF-1, using a variety of biophysical techniques including multidimensional NMR spectroscopy. AMX binds to FGF-1 and enhances its conformational stability. AMX binds to locations close to Cys30 and sterically blocks Cu(2+)-induced oxidation, leading to the formation of the homodimer of FGF-1. AMX-induced inhibition of the formation of the FGF-1 homodimer is observed both under cell-free conditions and in living cells. Results of this study suggest a novel approach for the design of drugs against FGF-1-mediated disorders.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amlexanox	Fibroblast growth factor 1	Protein	Humans	Unknown	Inhibitor	Details