Peptide Crosslinking by a Class of Plant Copper Enzymes

BURP domain peptide cyclases, or BpCs (an abbreviation we recommend in this opinion), are an emerging class of copper enzymes which catalyze the oxidative macrocyclization of peptides in plants. A close examination of their novel protein fold, along with the unique dicopper active site that meticulously controls crosslinking within peptides, highlights how nature exploits intricate mechanistic strategies to achieve diverse functionalities. Here, we summarize recent discoveries regarding the sequence, structure, function, and proposed chemistry of BpCs. We also present plausible mechanistic ideas and recommend important structural considerations that could advance investigations and discussions surrounding their reactivity and underlying mechanisms.