AUTHOR=Juhász János , Gáspári Zoltán , Pongor Sándor 

TITLE=Structure and Oxidative Folding of AAI, the Major Alfa-Amylase Inhibitor From Amaranth Seeds

JOURNAL=Frontiers in Chemistry

VOLUME=Volume 8 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2020.00180

DOI=10.3389/fchem.2020.00180

ISSN=2296-2646

ABSTRACT=AAI, the major alpha-amylase inhibitor (AAI) present in the seeds of the Mexican crop plant Amaranthus hypocondriacus is a 32-residue-long polypeptide with three disulfide bridges. Its structure is most closely related to the plant amylase inhibitor subfamily of knottins characterized by a topological knot formed by one disulfide bridge threading through a loop formed by the peptide chain as well as a short three-stranded beta sandwich core. AAI is specific against insect amylases and does not act on corresponding human or mammalian enzymes. The oxidative folding of AAI seems to follow a hirudine-like pathway with many non-native intermediates, but notably it proceeds through a major folding intermediate that contains a vicinal disulfide bridge. We think that MFI is a kinetic trap corresponding to a compact molten globule-like state of the peptide