Premium
Synthesis of PAF, an Antifungal Protein from P. chrysogenum , by Native Chemical Ligation: Native Disulfide Pattern and Fold Obtained upon Oxidative Refolding
Author(s) -
Váradi Györgyi,
Tóth Gábor K.,
Kele Zoltán,
Galgóczy László,
Fizil Ádám,
Batta Gyula
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201301098
Subject(s) - oxidative folding , native chemical ligation , disulfide bond , chemistry , protein folding , native state , antifungal , oxidative phosphorylation , biochemistry , folding (dsp implementation) , protein tertiary structure , biophysics , stereochemistry , combinatorial chemistry , protein disulfide isomerase , chemical synthesis , biology , microbiology and biotechnology , in vitro , electrical engineering , engineering
The folding of disulfide proteins is of considerable interest because knowledge of this may influence our present understanding of protein folding. However, sometimes even the disulfide pattern cannot be unequivocally determined by the available experimental techniques. For example, the structures of a few small antifungal proteins (PAF, AFP) have been disclosed recently using NMR spectroscopy but with some ambiguity in the actual disulfide pattern. For this reason, we carried out the chemical synthesis of PAF. Probing different approaches, the oxidative folding of the synthetic linear PAF yielded a folded protein that has identical structure and antifungal activity as the native PAF. In contrast, unfolded linear PAF was inactive, a result that may have implications concerning its redox state in the mode of action.