High‐Resolution Crystal Structure of a Lasso Peptide

Abstract

Lasso peptides are a group of a growing class of bioactive peptides of microbial origin. The first crystal structure of a member of this family, the glucagon receptor antagonist BI-32169, shows that the fold is built predominantly by regular secondary structural elements and a tight network of hydrogen bonds that are partially shielded from solvent by hydrophobic amino acid side chains. This results in an extraordinary stable structure that is resistant to thermal unfolding or proteolytic digestion, which facilitates its biological function.