Bicupins

Bicupins are proteins within the cupin superfamily characterized by having two cupin-type beta-barrel domains arranged in tandem within a single polypeptide. The bicupin architecture contrasts with monocupins, which contain a single cupin domain.

Each domain is typically about 100 amino acids and folds into the compact beta-barrel fold common to cupins. The two domains may be highly similar or diverged, and in many bicupins the remains of catalytic residues in one domain differ from those in the other, implying domain specialization. The proteins may form multimers such as homodimers or heterodimers, contributing to stability or substrate channeling.

Distribution: Bicupins have been found across bacteria, fungi, and plants, with notable representation in plant seeds where cupin-related storage proteins are abundant. They are frequently annotated in genome sequences based on their two-domain architecture.

Function: The bicupin fold supports a range of biochemical activities, including oxidation, hydrolysis, and isomerization, depending on the bound metal ion and active-site residues. Some bicupins act as dioxygenases or hydrolases, while others may serve non-enzymatic roles such as storage or structural scaffolding.

Evolution and significance: The two-domain arrangement is generally interpreted as a gene-duplication event followed by divergence, enabling novel functions while preserving structural stability. Bicupins provide insight into the evolution of the cupin superfamily and are of interest for protein engineering and biotechnological applications.