Molecular mechanism of inhibition of nonclassical FGF-1 export.
Article Details
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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]
- 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 UnknownInhibitorDetails